2024-03-29T14:46:40Zhttps:/www.ncbi.nlm.nih.gov/pmc/oai/oai.cgioai:pubmedcentral.nih.gov:1310252002-11-15medimmpmc-open
Medical immunology: a new journal for a new subspecialty
Smith, Kendall A
Med Immunol
Editorial
BioMed Central
2002-09-30
/pmc/articles/PMC131025/
/pubmed/12437786
http://dx.doi.org/10.1186/1476-9433-1-1
Text
en
Copyright © 2002 Smith; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1494052003-02-25medimmpmc-open
DNA array analysis of interleukin-2-regulated immediate/early genes
Beadling, Carol
Smith, Kendall A
Med Immunol
Research
BACKGROUND: Lymphocyte activation culminates in blastogenesis, cell cycle progression, DNA replication and mitosis. These complex cellular changes are programmed almost simultaneously by multiple ligands and receptors that trigger specific signal transduction pathways and transcription factors. Until now, the discovery of the genes regulated by each ligand/receptor pair has been hampered by the technologies available. RESULTS: To identify interleukin-2 (IL-2)-responsive genes, human peripheral blood mononuclear cells (PBMC) were pre-activated with anti-CD3, rested, and restimulated with IL-2 for 4 hr. Gene expression was analyzed using Affymetrix U95Av2 oligonucleotide arrays. To determine the most stringent parameters to score a gene as a bona fide IL-2 target, the expression of 19 known IL-2-regulated genes was examined first. All were induced at least 2-fold, with a difference in fluorescent intensity of ≥ 100 at p < 0.05. An additional 53 unique genes met these criteria. To determine which of these were immediate/early IL-2 targets in T cells, purified T cells were stimulated with IL-2 for 4 hr in the presence of cycloheximide to prevent secondary gene expression. Of the 72 genes identified in PBMCs, 20 were detected as immediate/early IL-2-regulated genes in purified T cells. In addition, 27 unique genes were IL-2-regulated in T cells but not in PBMCs. CONCLUSIONS: For a successful reductionist approach to the analysis of gene expression in lymphocyte activation, it is necessary to examine purified cell populations and immediate/early gene expression regulated by each ligand/receptor pair involved. This approach should allow the discovery of genes regulated by all of the ligand/receptor pairs involved in lymphocyte activation.
BioMed Central
2002-11-18
/pmc/articles/PMC149405/
/pubmed/12459040
http://dx.doi.org/10.1186/1476-9433-1-2
Text
en
Copyright © 2002 Beadling and Smith; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1494062003-02-25medimmpmc-open
Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy
Khanna, Ashwani
Plummer, Matthew
Bromberek, Katherine
Woodliff, Jeffrey
Hariharan, Sundaram
Med Immunol
Research
BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL. Blood was drawn on day zero and 14 days post treatment. Lymphocyte proliferation was quantified by (3)H-thymidine uptake assay (results expressed as counts per minute). The mRNA expression was studied by RT-PCR and serum levels of cytokines were quantified by ELISA and a cytokine bead array system. RESULTS: Lymphocyte proliferative response to PHA (p < 0.05), Con A (p < 0.006) and Anti-CD3 (p <0.005) were significantly decreased in patients who received both TAC and SRL compared to TAC alone. The mRNA expression of proinflammatory cytokines TNF-α (p < 0.05), cyclins G (p < 0.01) and E (p < 05) were decreased, and of TGF-β (p < 0.03) and p21 (p < 0.05) were increased in patients treated with this combination. Circulating levels of IFN-γ (p < 0.04), IL-4 (p < 0.02), and Il-2 (p < 0.03) were significantly inhibited and elevation of TGF-β (p < 0.04) was observed in patients treated with TAC and SRL combination. CONCLUSION: These novel findings demonstrate that addition of SRL to TAC therapy enhances immuno modulation and causes increased immunosuppression providing a rationale for this concomitant therapy.
BioMed Central
2002-11-19
/pmc/articles/PMC149406/
/pubmed/12495444
http://dx.doi.org/10.1186/1476-9433-1-3
Text
en
Copyright © 2002 Khanna et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1494072003-02-25medimmpmc-open
Optimal clinical trial designs for immune-based therapies in persistent viral infections
Smith, Kendall A
Med Immunol
Commentary
There is now effective therapy for infection by the Human Immunodeficiency Virus (HIV), but there is no cure. Consequently, antiviral drugs must be administered continuously to suppress viral replication. Recently, a large phase III international immune-based therapy trial was discontinued because it is difficult to measure clinical endpoints while antivirals are administered. Since the immune system has evolved under the selective force of microbial infections, the immune reaction is antiviral. This commentary explores the rationale of using "Diagnostic Treatment Interruptions" of antiviral therapies to determine efficacies of immune-based therapies.
BioMed Central
2002-11-21
/pmc/articles/PMC149407/
/pubmed/12459051
http://dx.doi.org/10.1186/1476-9433-1-4
Text
en
Copyright © 2002 Smith; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1512752003-03-13medimmpmc-open
New insights into the possible role of bacteriophages in host defense and disease
Gorski, Andrzej
Dabrowska, Krystyna
Switala-Jeleń, Kinga
Nowaczyk, Maria
Weber-Dabrowska, Beata
Boratynski, Janusz
Wietrzyk, Joanna
Opolski, Adam
Med Immunol
Hypothesis
BACKGROUND: While the ability of bacteriophages to kill bacteria is well known and has been used in some centers to combat antibiotics – resistant infections, our knowledge about phage interactions with mammalian cells is very limited and phages have been believed to have no intrinsic tropism for those cells. PRESENTATION OF THE HYPOTHESIS: At least some phages (e.g., T4 coliphage) express Lys-Arg-Gly (KGD) sequence which binds β3 integrins (primarily αIIbβ3). Therefore, phages could bind β3+ cells (platelets, monocytes, some lymphocytes and some neoplastic cells) and downregulate activities of those cells by inhibiting integrin functions. TESTING THE HYPOTHESIS: Binding of KGD+ phages to β3 integrin+ cells may be detected using standard techniques involving phage – mediated bacterial lysis and plaque formation. Furthermore, the binding may be visualized by electron microscopy and fluorescence using labelled phages. Binding specificity can be confirmed with the aid of specific blocking peptides and monoclonal antibodies. In vivo effects of phage – cell interactions may be assessed by examining the possible biological effects of β3 blockade (e.g., anti-metastatic activity). IMPLICATION OF THE HYPOTHESIS: If, indeed, phages can modify functions of β3+ cells (platelets, monocytes, lymphocytes, cancer cells) they could be important biological response modifiers regulating migration and activities of those cells. Such novel understanding of their role could open novel perspectives in their potential use in treatment of cardiovascular and autoimmune disease, graft rejection and cancer.
BioMed Central
2003-02-14
/pmc/articles/PMC151275/
/pubmed/12625836
http://dx.doi.org/10.1186/1476-9433-2-2
Text
en
Copyright © 2003 Gorski et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:1515982003-03-20medimmpmc-open
The HIV vaccine saga
Smith, Kendall A
Med Immunol
Commentary
The development of a vaccine that can prevent infection by the Human immunodeficiency virus or prevent the Acquired Immunodeficiency Syndrome has remained elusive despite 20 years of scientific effort. This "Commentary" analyzes the reasons that the development of a vaccine has been so difficult, and proposes a plan to work towards an immunological approach to investigate the best vaccine candidates in the first world in individuals who are already infected, before taking the most promising vaccines to the developing world to attempt to prevent infection and disease. SAGA: (Old Norse) "a long, continued heroic story that is action-packed, but not especially romantic, and that is historical or legendary or both".
BioMed Central
2003-02-14
/pmc/articles/PMC151598/
/pubmed/12628020
http://dx.doi.org/10.1186/1476-9433-2-1
Text
en
Copyright © 2003 Smith; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:4193692004-05-28medimmpmc-open
NF-kB inhibitor blocks B cell development at two checkpoints
Feng, Biao
Cheng, Shuhua
Pear, Warren S
Liou, Hsiou-Chi
Med Immunol
Research
Members of the NF-kB transcription factor family are differentially expressed in the B cell lineage. Disruption of individual or two NF-kB subunits exhibits distinct defects in B lymphocyte development, activation, and survival. However, the role each NF-kB plays during B cell development has been obscured by molecular compensation. To address this issue, a trans-dominant form of IkBα was transduced into bone marrow cells to act as a pan-inhibitor of NF-kB using a retroviral system. While the development of T-lymphocytes and myeloid cell lineages was not grossly affected by the transduced IkBα gene, a significant reduction in the number and percentage of B lineage cells was apparent in IkBα transduced chimeric mice. IkBα expression decreased the percentage of pre-B and immature B cell subsets in the bone marrow and further impaired the development of follicular mature B cells and marginal zone B cells in the periphery. Introduction of the Bcl-X transgene completely restored the pre-B and immature B cell pool in the bone marrow. However, despite a significant improvement of overall viability of the B cell lineage, Bcl-X expression was insufficient to overcome the maturation block resulting from NF-kB inhibition. Together, our study suggests that NF-kB activity is required for two distinct checkpoints during B cell development: one is for pre-B/immature B cell viability, the other is to provide both survival and maturation signals to ensure the proper development of follicular mature B cells.
BioMed Central
2004-03-29
/pmc/articles/PMC419369/
/pubmed/15050028
http://dx.doi.org/10.1186/1476-9433-3-1
Text
en
Copyright © 2004 Feng et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
oai:pubmedcentral.nih.gov:5443982005-01-14medimmpmc-open
New approaches to eliciting protective immunity through T cell repertoire manipulation: the concept of thymic vaccination
Fridkis-Hareli, Masha
Reinherz, Ellis L
Med Immunol
Commentary
Conventional vaccines afford protection against infectious diseases by expanding existing pathogen-specific peripheral lymphocytes, both CD8 cytotoxic effector (CTL) and CD4 helper T cells. The latter induce B cell maturation and antibody production. As a consequence, lymphocytes within the memory pool are poised to rapidly proliferate at the time of a subsequent infection. The "thymic vaccination" concept offers a novel way to alter the primary T cell repertoire through exposure of thymocytes to altered peptide ligands (APL) with reduced T cell receptor (TCR) affinity relative to cognate antigens recognized by those same TCRs. Thymocyte maturation (i.e. positive selection) is enhanced by low affinity interaction between a TCR and an MHC-bound peptide in the thymus and subsequent emigration of mature cells into the peripheral T lymphocyte pool follows. In principal, such variants of antigens derived from infectious agents could be utilized for peptide-driven maturation of thymocytes bearing pathogen-specific TCRs. To test this idea, APLs of gp(33–41), a D(b)-restricted peptide derived from the lymphocytic choriomeningitis virus (LCMV) glycoprotein, and of VSV8, a K(b)-restricted peptide from the vesicular stomatitis virus (VSV) nucleoprotein, have been designed and their influence on thymic maturation of specific TCR-bearing transgenic thymocytes examined in vivo using irradiation chimeras. Injection of APL resulted in positive selection of CD8 T cells expressing the relevant viral specificity and in the export of those virus-specific CTL to lymph nodes without inducing T cell proliferation. Thus, exogenous APL administration offers the potential of expanding repertoires in vivo in a manner useful to the organism. To efficiently peripheralize antigen-specific T cells, concomitant enhancement of mechanisms promoting thymocyte migration appears to be required. This commentary describes the rationale for thymic vaccination and addresses the potential prophylactic and therapeutic applications of this approach for treatment of infectious diseases and cancer. Thymic vaccination-induced peptide-specific T cells might generate effective immune protection against disease-causing agents, including those for which no effective natural protection exists.
BioMed Central
2004-12-08
/pmc/articles/PMC544398/
/pubmed/15588284
http://dx.doi.org/10.1186/1476-9433-3-2
Text
en
Copyright © 2004 Fridkis-Hareli and Reinherz; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5448502005-01-21medimmpmc-open
The quantal theory of how the immune system discriminates between "self and non-self"
Smith, Kendall A
Med Immunol
Review
In the past 50 years, immunologists have accumulated an amazing amount of information as to how the immune system functions. However, one of the most fundamental aspects of immunity, how the immune system discriminates between self vs. non-self, still remains an enigma. Any attempt to explain this most intriguing and fundamental characteristic must account for this decision at the level of the whole immune system, but as well, at the level of the individual cells making up the immune system. Moreover, it must provide for a molecular explanation as to how and why the cells behave as they do. The "Quantal Theory", proposed herein, is based upon the "Clonal Selection Theory", first proposed by Sir McFarland Burnet in 1955, in which he explained the remarkable specificity as well as diversity of recognition of everything foreign in the environment. The "Quantal Theory" is built upon Burnet's premise that after antigen selection of cell clones, a proliferative expansion of the selected cells ensues. Furthermore, it is derived from experiments which indicate that the proliferation of antigen-selected cell clones is determined by a quantal, "all-or-none", decision promulgated by a critical number of cellular receptors triggered by the T Cell Growth Factor (TCGF), interleukin 2 (IL2). An extraordinary number of experiments reported especially in the past 20 years, and detailed herein, indicate that the T cell Antigen Receptor (TCR) behaves similarly, and also that there are several critical numbers of triggered TCRs that determine different fates of the T cells. Moreover, the fates of the cells appear ultimately to be determined by the TCR triggering of the IL2 and IL2 receptor (IL2R) genes, which are also expressed in a very quantal fashion. The "Quantal Theory" states that the fundamental decisions of the T cell immune system are dependent upon the cells receiving a critical number of triggered TCRs and IL2Rs and that the cells respond in an all-or-none fashion. The "Quantal Theory" accounts fully for the development of T cells in the thymus, and such fundamental cellular fates as both "positive" and "negative" selection, as well as the decision to differentiate into a "Regulatory T cell" (T-Reg). In the periphery, the "Quantal Theory" accounts for the decision to proliferate or not in response to the presence of an antigen, either non-self or self, or to differentiate into a T-Reg. Since the immune system discriminates between self and non-self antigens by the accumulated number of triggered TCRs and IL2Rs, therapeutic manipulation of the determinants of these quantal decisions should permit new approaches to either enhance or dampen antigen-specific immune responses.
BioMed Central
2004-12-17
/pmc/articles/PMC544850/
/pubmed/15606917
http://dx.doi.org/10.1186/1476-9433-3-3
Text
en
Copyright © 2004 Smith; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5506742005-02-27medimmpmc-open
FADD adaptor in cancer
Tourneur, Léa
Buzyn, Agnès
Chiocchia, Gilles
Med Immunol
Review
FADD (Fas Associated protein with Death Domain) is a key adaptor molecule transmitting the death signal mediated by death receptors. In addition, this multiple functional protein is implicated in survival/proliferation and cell cycle progression. FADD functions are regulated via cellular sublocalization, protein phosphorylation, and inhibitory molecules. In the present review, we focus on the role of the FADD adaptor in cancer. Increasing evidence shows that defects in FADD protein expression are associated with tumor progression both in mice and humans. Better knowledge of the mechanisms leading to regulation of FADD functions will improve understanding of tumor growth and the immune escape mechanisms, and could open a new field for therapeutic interventions.
BioMed Central
2005-02-17
/pmc/articles/PMC550674/
/pubmed/15717929
http://dx.doi.org/10.1186/1476-9433-4-1
Text
en
Copyright © 2005 Tourneur et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:5547562005-03-18medimmpmc-open
The Future of Smallpox Vaccination: is MVA the key?
Slifka, Mark K
Med Immunol
Commentary
Eradication of the smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of smallpox vaccination has gained renewed attention due to the potential risk that smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity.
BioMed Central
2005-03-01
/pmc/articles/PMC554756/
/pubmed/15740619
http://dx.doi.org/10.1186/1476-9433-4-2
Text
en
Copyright © 2005 Slifka; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10799322005-04-15medimmpmc-open
The Classics of Immunology
Smith, Kendall A
Med Immunol
Editorial
Medical Immunology will be publishing invited Reviews and Commentaries from investigators who are at the forefront of their fields, to up-date our readers as to the current state of their art. These Reviews and Commentaries will be accompanied by Editorials that place the current work into the perspective of the first contribution in an area, which resulted in a "Classic" paper. Where possible, links will be provided to the original publication, so that the modern student of immunology can read the original and draw their own conclusions as to the value of the "Classic" contribution, and its relationship to our contemporary views as to how the immune system functions. To begin this process at the very dawn of immunology, we highlight Sir Edward Jenner's first descriptions of the use of cowpox to immunize individuals against the dread disease smallpox.
BioMed Central
2005-03-10
/pmc/articles/PMC1079932/
/pubmed/15760473
http://dx.doi.org/10.1186/1476-9433-4-3
Text
en
Copyright © 2005 Smith; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10799332005-04-15medimmpmc-open
Anthrax vaccine design: strategies to achieve comprehensive protection against spore, bacillus, and toxin
Wang, Julia Y
Roehrl, Michael H
Med Immunol
Review
The successful use of Bacillus anthracis as a lethal biological weapon has prompted renewed research interest in the development of more effective vaccines against anthrax. The disease consists of three critical components: spore, bacillus, and toxin, elimination of any of which confers at least partial protection against anthrax. Current remedies rely on postexposure antibiotics to eliminate bacilli and pre- and postexposure vaccination to target primarily toxins. Vaccines effective against toxin have been licensed for human use, but need improvement. Vaccines against bacilli have recently been developed by us and others. Whether effective vaccines will be developed against spores is still an open question. An ideal vaccine would confer simultaneous protection against spores, bacilli, and toxins. One step towards this goal is our dually active vaccine, designed to destroy both bacilli and toxin. Existing and potential strategies towards potent and effective anthrax vaccines are discussed in this review.
BioMed Central
2005-03-24
/pmc/articles/PMC1079933/
/pubmed/15790405
http://dx.doi.org/10.1186/1476-9433-4-4
Text
en
Copyright © 2005 Wang and Roehrl; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:10878732005-04-30medimmpmc-open
Wanted, an Anthrax vaccine: Dead or Alive?
Smith, Kendall A
Med Immunol
Editorial
It has been more than 100 years since the realization that microbes are capable of causing disease. In that time, we have learned a great deal as to how each organism has adapted to the immune system so as to avoid elimination. As well, we have also learned an immense amount since Louis Pasteur first proposed that the solution to infectious diseases was to culture the microbes and attenuate their virulence, so as to use them as vaccines. From the optimism and promise of the 19(th )century and immunization as the ultimate answer to the invasion by the microbial world, to the scientific realities of the 21(st )century, it is of interest to retrace the steps of the earliest microbiologists cum immunologists, to realize how far we've come, as well as how far we yet have to go. This editorial focuses on the history of anthrax as a microbial disease, and the earliest efforts at producing a vaccine for its prevention.
BioMed Central
2005-04-18
/pmc/articles/PMC1087873/
/pubmed/15836780
http://dx.doi.org/10.1186/1476-9433-4-5
Text
en
Copyright © 2005 Smith; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:11319192005-05-20medimmpmc-open
The continuing HIV vaccine saga: naked emperors alongside fairy godmothers
Smith, Kendall A
Med Immunol
Commentary
The latest developments in the HIV vaccine field were aired at a Keystone Symposium recently. This Commentary summarizes some of the highlights from this meeting, and focuses on some of the developments that appeared particularly promising, as well as those that do not. Unfortunately, the "saga" continues.
BioMed Central
2005-05-06
/pmc/articles/PMC1131919/
/pubmed/15877816
http://dx.doi.org/10.1186/1476-9433-4-6
Text
en
Copyright © 2005 Smith; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:14888372006-07-06medimmpmc-open
The continuing HIV vaccine saga: is a paradigm shift necessary?
Smith, Kendall A
Med Immunol
Editorial
As pointed out in previous editorials, the development of an effective vaccine for the Human Immunodeficiency Virus capable of preventing infection, or even one capable of preventing the Acquired Immunodeficiency Disease Syndrome, has eluded investigators for the past 20 years. Now Reche and Keskin and their co-workers have provided evidence that an entirely new approach, based upon modern bioinformatics methods and skillful in vitro immunological experiments, may result in an effective way to prime the T cell immune response of normal individuals against conserved peptide epitopes.
BioMed Central
2006-05-18
/pmc/articles/PMC1488837/
/pubmed/16709246
http://dx.doi.org/10.1186/1476-9433-5-2
Text
en
Copyright © 2006 Smith; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15596202006-09-02medimmpmc-open
Elicitation from virus-naive individuals of cytotoxic T lymphocytes directed against conserved HIV-1 epitopes
Reche, Pedro A
Keskin, Derin B
Hussey, Rebecca E
Ancuta, Petronela
Gabuzda, Dana
Reinherz, Ellis L
Med Immunol
Research
Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population protection coverage (PPC) was computed and epitope pools assembled. Strikingly, only a minority of immunocompetent HIV-1 infected individuals responds to pools with PPC >95%. In contrast, virus-naive individuals uniformly expand IFNγ producing cells and mount anti-HIV-1 cytolytic activity. This disparity suggests a vaccine design paradigm shift from infected to normal subjects.
BioMed Central
2006-05-18
/pmc/articles/PMC1559620/
/pubmed/16674822
http://dx.doi.org/10.1186/1476-9433-5-1
Text
en
Copyright © 2006 Reche et al; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15624222006-09-08medimmpmc-open
The structure of IL2 bound to the three chains of the IL2 receptor and how signaling occurs
Smith, Kendall A
Med Immunol
Review
The interleukin-2 molecule and receptor were the first of the interleukins to be discovered and characterized at the molecular level. Now after 20 years of effort, two groups have succeeded in determining the structure of IL2 bound to the external domains of the three receptor chains in a quaternary complex. What do we know now that we did not know before this structural information was available, and how do these new data help us to develop new therapies?
BioMed Central
2006-08-14
/pmc/articles/PMC1562422/
/pubmed/16907989
http://dx.doi.org/10.1186/1476-9433-5-3
Text
en
Copyright © 2006 Smith; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
oai:pubmedcentral.nih.gov:15920972006-10-05medimmpmc-open
Chronic Granulomatous Disease; fundamental stages in our understanding of CGD
Assari, Tracy
Med Immunol
Review
It has been 50 years since chronic granulomatous disease was first reported as a disease which fatally affected the ability of children to survive infections. Various milestone discoveries from the insufficient ability of patients' leucocytes to destroy microbial particles to the underlying genetic predispositions through which the disease is inherited have had important consequences. Longterm antibiotic prophylaxis has helped to fight infections associated with chronic granulomatous disease while the steady progress in bone marrow transplantation and the prospect of gene therapy are hailed as long awaited permanent treatment options. This review unearths the important findings by scientists that have led to our current understanding of the disease.
BioMed Central
2006-09-21
/pmc/articles/PMC1592097/
/pubmed/16989665
http://dx.doi.org/10.1186/1476-9433-5-4
Text
en
Copyright © 2006 Assari; licensee BioMed Central Ltd.
http://creativecommons.org/licenses/by/2.0
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.