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Detection And Characterization Of Hiv 1 Specific T Cell Responses Amongst Exposed And Unexposed Hiv 1 Seronegative Individuals
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Book Synopsis Detection and Characterization of HIV-1 Specific T Cell Responses Amongst Exposed and Unexposed HIV-1 Seronegative Individuals by : Suzanne L. Campion
Download or read book Detection and Characterization of HIV-1 Specific T Cell Responses Amongst Exposed and Unexposed HIV-1 Seronegative Individuals written by Suzanne L. Campion and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The primary aim of this thesis was to examine whether HIV -1 specific T cell responses in HIV -1 exposed seronegative (HESN) subjects could be firstly detected and if so, conferred protection against productive infection from HIV -1. Cultured IFN-y ELISpot found 38.7-60% of HESN subjects had detectable HIV-1 specific T cell responses. HIV -1 specific T cell responses could be titrated, were typically mediated by CD4+ T cells and tended to map to previously defined, promiscuous epitopes. In a statistically powered, retrospective study, no evidence was found to support a role for pre-existing HIV -1 specific T cell responses in either protection against or risk of HIV -1 infection. Exposure to HIV -1 impacted upon detection of pre-existing HIV -1 specific T cell responses, in terms of frequency (p=0.01), magnitude (p=0.02) and maintenance of response. This suggests, that exposure to HIV-1 was truly priming HIV-1 specific T cell responses. However, exposure to HIV -1 was not a prerequisite and HIV-1 specific T cell responses were detectable amongst HIV -1 unexposed seronegative (HUSN) donors. Similar to HESN, HIV-1 specific T cell responses detected amongst HUSN, could be mapped to the peptide level, titrated and were predominately mediated by CD4+ T cells. These T cells were shown to be detectable amongst memory CD4+ T cell subsets, suggesting they were not the result of in vitro priming. Whilst sample size was low, HIV-1 specific T cell responses, detected amongst HUSN donors were shown to be oligoclonal in TCRV~ usage. The detection of memory CD4+ HIV -1 specific T cell responses amongst HUSN opens a broader debate about the ontogeny of HIV -1 specific T cell responses, the inherent properties of the adaptive immune system and its preponderance toward degeneracy and cross reactivity. Greater understanding of these fundamental immunology questions should, improve our understanding of T cell ontogeny and hopefully prove beneficial in the design of a novel therapeutic vaccine for HIV -1.
Book Synopsis Characteristics of HIV-1 Specific T Cell Responses in Healthy, HIV-1 Negative Vaccine Recipients by : Nicola Winstone
Download or read book Characteristics of HIV-1 Specific T Cell Responses in Healthy, HIV-1 Negative Vaccine Recipients written by Nicola Winstone and published by . This book was released on 2008 with total page 648 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Antigen-specific T-cell Response to HIV-1 Infection by : Michael Scott Killian
Download or read book The Antigen-specific T-cell Response to HIV-1 Infection written by Michael Scott Killian and published by . This book was released on 2002 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Dynamic Interplay Between HIV-1 and T Cells by : Christian Raul Aguilera-Sandoval
Download or read book The Dynamic Interplay Between HIV-1 and T Cells written by Christian Raul Aguilera-Sandoval and published by . This book was released on 2016 with total page 199 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although it is well-documented that T cells are crucial in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) yet the dynamic interplay between HIV-1 and T cells has not been fully elucidated. The effects that HIV-1 has on T cell diversity and the effects that T cell diversity has on HIV viral escape have not been well characterized; an understanding of these effects could have crucial implications for design of CTL vaccines. In particular, such information could provide insights needed to develop methods for reconstitution of sufficient diversity in the immune systems of HIV+ persons to allow CTL vaccines to be effective. Furthermore, such information could be helpful in the development of CTL vaccines against semi-conserved epitopes, so as to prevent viral escape. These are the aims this dissertation will attempt to address. One major problem with the current approach to HIV-1 vaccine development is that the strategies currently being employed ultimately fail; this is mostly, but not entirely, due to HIV-1's high rate of mutation. This ultimately results in the escape of the virus from vaccine-induced immunity, thereby rendering such vaccines useless. Both CD4+ and CD8+ T cells play a major role in immune responses to HIV-1. However, during the course of infection, CD4+ T cells are depleted, not only in number, but also in diversity. Limited CD4+ T cell diversity cripples the immune system, as such CD4+ T cells are not able to provide the help necessary for effective innate and adaptive immune system responses to HIV, including help to CTL, which is of particular importance for this dissertation. CTL responses constitute one of the crucial arms of the immune system that is highly responsible for responding to HIV-1 infection. However, immune defenses mediated by CTL ultimately fail in HIV infection, which is, again, also largely (but not entirely) due to high rates of HIV-1 mutation that cause constant viral escape, which, in turn, drives chronic immune activation and ultimately CTL exhaustion. We have addressed each of these problems in this dissertation. In Chapter Two, we present results of studies in which we examined thymic output and CD4+ T cell diversity from HIV+ persons who were perinatally infected, were in treatment and had lived with the infection for over two decades. In Chapter Three, we present results of studies in which we screened for CTL responses against the gag 162-173 KAFSPEVIPMF epitope from multiple persons and identified and cloned the TCR responsible for these responses, using a novel technique TCR identification and cloning technique that we also present in this chapter. Finally, we functionally tested the cloned KF11-specific TCR to confirm that this panel was able to recognize and lyse the most common circulating variants of the KF11 epitope. The results presented in Chapter Two of this dissertation show that HIV+ participants had reduced CD4+ T cell levels, with predominant depletion of the memory subset, but preservation of naive cells. In most of these HIV+ participants, levels of CD4+ T cells that were recent thymic emigrants' CD4+ T cell levels were normal, and enhanced thymopoiesis was present, as indicated by higher proportions of CD4+ T cells containing TCR recombination excision circles. Memory CD4+ T cell depletion was highly associated with CD8+ T-cell activation in HIV-1- infected persons, and plasma interlekin-7 levels were correlated with levels of naive CD4+ T cells, suggesting activation-driven loss and compensatory enhancement of thymopoiesis. Deep sequencing of CD4+ T cell receptor sequences in HIV+ subjects who had high levels of compensatory enhancement of thymopoiesis revealed supranormal TCR diversity, providing additional evidence of enhanced thymic output. In Chapter Three we introduce and describe an inexpensive new technique to quickly and efficiently identify, clone and functionally test epitope-specific TCR. Using this new technique and samples from multiple HIV+ HLA-B*5701 persons, we identified, cloned and functionally tested four KF11-specific TCR. The four identified KF11-specific TCR were able to recognize and lyse target cells that were peptide-loaded with the six most common circulating variants of KF11. These six variants make up 97% of all circulating variants, according to the Los Alamos HIV database. The functional avidity and killing efficiency of the KF11-specific TCR were also investigated. Consonant with prior supporting data on KF11-specific TCR, the functional avidity observed for these four KF11-specific TCR had a range of 89 ng/ml to 832 ng/ml. One of the KF11-specific TCR was tested for its ability to lyse HIV-infected cells. This TCR was able to lyse cells infected with three of the four variants that were previously recognized and lysed in the peptide-loaded target cells. If these TCR are validated in vivo, and they are to prevent viral escape, the process could be repeated with other HLA restricted epitopes in order to develop a new treatment against HIV-1.
Book Synopsis Identification and Characterization of Immunologically Relevant CD8+ T Cell Epitopes of HIV-1 Nef Protein by : Elnaz Shadabi
Download or read book Identification and Characterization of Immunologically Relevant CD8+ T Cell Epitopes of HIV-1 Nef Protein written by Elnaz Shadabi and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: HIV-1 mutates to escape HLA Class I restricted CD8+ T cells. Positively selected mutations (PSMs) are amino acid substitutions that allow the virus to survive under host immune pressure. However, the impact of PSMs on host clinical outcomes remains unknown. Negative effector (Nef), an accessory protein of HIV-1, enhances the pathogenicity and replication of the virus by down-regulating CD4 and HLA Class I expression from host cell surface to avoid recognition by immune cells, and modification of host cell signal transduction pathways to ensure a persistent state of infection. In both human and macaque models of infection some Nef-specific CD8+ T cell responses that drive viral mutations have been associated with better immune control. In this study, we identified PSMs within HIV-1 Nef, and analyzed their association with host immune selection pressure, and their potential impact on host disease status. We hypothesized that CD8+ T cell epitopes in HIV-1 Nef protein contain PSMs that are associated with different clinical outcomes in the infected host. HIV-1 nef gene was sequenced using 454 sequencing technology from 508 HIV-positive samples of the Pumwani sex-workers cohort of Nairobi, Kenya. PSMs in Nef were identified using bioinformatics tool, Quasi analysis and correlated with disease progression data. Three PSMs were associated with faster CD4 decline (E63D p=0.028, log rank: 4.799; I101V p=0.003, log rank:8.667 and I168M p=0.042, log rank:4.150), while two PSMs were associated with slower CD4 decline (H116N p=0.00011, log rank:14.891 and K182M p=0.03, log rank=4.753). Forty peptides containing a specific PSM were tested with ELISPOT assay, 27 of which were confirmed as CD8+ T cell epitopes. There was no significant difference in the frequency of antigen-specific CD8+ T cells with antiviral intracellular cytokines, their proliferation and exhaustion characteristics between peptides with PSMs associated with different disease progression status. However, the frequency of CD8+ T cells restricted by A*02:01-ILDLWVYNT (IT9-N) epitope, containing a PSM associated with slower CD4 decline, was higher (p0.0001) than CD8+ T cells restricted by A*02:01-ILDLWVYHT (IT9-H) epitope, containing consensus amino acid associated with faster CD4 decline. Identification of PSMs associated with different clinical outcomes and characterization of CD8+ T cell populations specific to these PSM containing epitopes can help to determine better immunogens for an effective HIV-1 vaccine.
Book Synopsis Characterization of HIV Specific T Cell Responses During Acute and Early HIV-1 Subtype C Infection by : Mandla Dennis Mlotshwa
Download or read book Characterization of HIV Specific T Cell Responses During Acute and Early HIV-1 Subtype C Infection written by Mandla Dennis Mlotshwa and published by . This book was released on 2013 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Qualitative Analysis of HIV-1-specific CD8 T Cell Responses by : Olusimidele Tolulope Akinsiku
Download or read book Qualitative Analysis of HIV-1-specific CD8 T Cell Responses written by Olusimidele Tolulope Akinsiku and published by . This book was released on 2011 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Longitudinal Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-specific CD8 T Cell Responses in a Cohort of Clade B-infected Patients of African and Mixed African Descent by : Debbie Jane Ruhl
Download or read book Longitudinal Analysis of Human Immunodeficiency Virus Type 1 (HIV-1)-specific CD8 T Cell Responses in a Cohort of Clade B-infected Patients of African and Mixed African Descent written by Debbie Jane Ruhl and published by . This book was released on 2004 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Investigation of Immune Quiescence by : Abdirahman Abdullahi
Download or read book Investigation of Immune Quiescence written by Abdirahman Abdullahi and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent research of a cohort of HIV exposed sero-negative (HESN) female commercial sex workers in Nairobi has revealed an Immune Quiescent phenotype; characterized by reduced T cell activation and higher regulatory T cells (Tregs) in peripheral blood. HESN women also express lower levels of interferon regulatory factor-1 (IRF-1), a critical regulator known to negatively impact Treg development in mice. In this study, we analyzed the functional capacity of Tregs by an in vitro depletion assay and measured functionality by flow cytometry. Data showed Tregs suppressed CD4+ and CD8+ proliferation responses. We characterized the link between Tregs and IRF-1 in HESN and observed an inverse correlation between IRF-1 expression and Treg proportions. We also established reduced expression of IRF-1 in Tregs of healthy donors by flow cytometry. In a separate study, flow cytometric analysis of high-risk sex-workers revealed that CTLA-4 expression in memory CD4+cells, not Treg frequency, was associated with HIV seroconversion.
Book Synopsis Analysis of Epitope-specific HIV CD8 T Cell Responses Elicited During Early HIV-1 Infection and Their Association with Viral Control by : Pratima Kunwar
Download or read book Analysis of Epitope-specific HIV CD8 T Cell Responses Elicited During Early HIV-1 Infection and Their Association with Viral Control written by Pratima Kunwar and published by . This book was released on 2012 with total page 133 pages. Available in PDF, EPUB and Kindle. Book excerpt: The enormity of global human immunodeficiency virus type 1 (HIV)/acquired immunodeficiency syndrome (AIDS) pandemic underscores the urgency to develop a safe, effective and accessible prophylactic AIDS vaccine. Multiple lines of evidence in humans and animal models have shown that HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL) are important in controlling and preventing HIV infection. However, the precise qualities of effective epitope-specific CD8+ CTL responses that may be responsible for control remain unclear. Several vaccine strategies have been designed to elicit CD8+ T cell responses against HIV. Previous T cell based vaccine candidates that have failed to offer protection and HIV control primarily induced HIV-1-specific T cells that targeted variable regions of HIV-1. Genetic studies have shown an association between specific human leukocyte antigens (HLAs), (notably HLA-B*27 and -B*57 allele groups) and slower rates of disease progression in the absence of anti-retroviral therapy (ART). HIV-1-specific CD8+ T cells restricted by these HLA alleles are dominant early in infection in individuals expressing these alleles, and predominantly target conserved regions of Gag. These data suggest that an effective T-cell based immunogen should contain conserved regions of HIV-1 as it will increase the likelihood that CD8+ T cells will recognize incoming viral species of diverse clades and decrease the likelihood of rapid escape variants against the recognized epitopes. We extend these observations to comprehensively identify all CD8+ T cell responses that are elicited during early infection. The central goal of this dissertation is to determine if conservation of the epitopes targeted during early HIV-1-infection play an important role on viral control. Here we demonstrate that individuals possessing CD8+ T cells recognizing conserved epitopes of the virus have lower viral load set point than those recognizing only variable epitopes. Collectively, our results imply that the next-generation of T cell based vaccines should focus on strategies that can induce CD8+ T cell responses specifically to conserved regions of HIV-1.
Book Synopsis Qualitative Characteristics of HIV-1-Specific CD4+ T Cells Responses Associated With Broadly Neutralizing Antibody Response by : Ika N. Kadariswantiningsih
Download or read book Qualitative Characteristics of HIV-1-Specific CD4+ T Cells Responses Associated With Broadly Neutralizing Antibody Response written by Ika N. Kadariswantiningsih and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The underlying mechanism responsible for the development of broadly neutralizing antibodies (bNAbs) in natural infection is poorly understood. Current findings suggest that a sufficient help of CD4+ T cells to B cells is required in the development of bNAbs. At the clinical level, it is unclear whether bNAbs generating individuals exhibit more robust HIV-1-specific CD4+ T cells responses, thereby providing better help to B cells during infection. We hypothesized bNAbs response generating individuals to possess superior qualitative characteristics in their HIV-1-specific CD4+ T cells responses compared to non-neutralizers. In this study, in vitro stimulation assay that allows the evaluation of the combined CD4-orchestrated cellular immune response to HIV-1 antigens was performed. CD8+ depleted peripheral blood mononuclear cells (PBMCs) of chronically HIV-infected subjects with different capability of generating bNAbs response were stimulated with Gag peptide pools for 48 hours. Qualitative characteristics of HIV-1-specific CD4+ T cells are analyzed based on 34 chemokines and cytokines secretion in the supernatant. HIV-1-specific CD4+ T cells from broad neutralizers showed to have a unique capacity to stimulate production of the cardinal cytokine CXCL13 that has been previously associated with germinal center formation and development of broadly neutralizing antibodies against HIV. Linear discriminant analysis (LDA) and partial least square discriminant analysis (PLSDA) also showing CXCL13 to be positively correlated with neutralization. Immunofluorescence staining of the lymph node section showed that CXCL13 was exclusively found in the follicle. Although CXCL13 is thought to be a natural ligand for CXCR5, not all cells that expressed CXCL13 have CXCR5 co-staining. It may suggest that CXCL13 is not exclusively expressed by CXCR5+ CD4+ T cells in the germinal centers and other follicular cell subset may contribute.
Book Synopsis Characterization of NK Cell Subsets Responding to HIV Infected Cells by : Irene Lisovsky
Download or read book Characterization of NK Cell Subsets Responding to HIV Infected Cells written by Irene Lisovsky and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Globally, over 36 million people are infected with human immunodeficiency virus type 1 (HIV-1). Some individuals exposed to HIV remain persistently seronegative. Among those who become infected a subset of approximately 5% progress to acquired immunodeficiency syndrome (AIDS) slowly, and even fewer, i.e.
Book Synopsis Viral Sexually Transmitted Diseases—Advances in Research and Treatment: 2012 Edition by :
Download or read book Viral Sexually Transmitted Diseases—Advances in Research and Treatment: 2012 Edition written by and published by ScholarlyEditions. This book was released on 2012-12-26 with total page 948 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral Sexually Transmitted Diseases—Advances in Research and Treatment: 2012 Edition is a ScholarlyEditions™ eBook that delivers timely, authoritative, and comprehensive information about Viral Sexually Transmitted Diseases. The editors have built Viral Sexually Transmitted Diseases—Advances in Research and Treatment: 2012 Edition on the vast information databases of ScholarlyNews.™ You can expect the information about Viral Sexually Transmitted Diseases in this eBook to be deeper than what you can access anywhere else, as well as consistently reliable, authoritative, informed, and relevant. The content of Viral Sexually Transmitted Diseases—Advances in Research and Treatment: 2012 Edition has been produced by the world’s leading scientists, engineers, analysts, research institutions, and companies. All of the content is from peer-reviewed sources, and all of it is written, assembled, and edited by the editors at ScholarlyEditions™ and available exclusively from us. You now have a source you can cite with authority, confidence, and credibility. More information is available at http://www.ScholarlyEditions.com/.
Book Synopsis SARS, MERS and other Viral Lung Infections by : David S. Hui
Download or read book SARS, MERS and other Viral Lung Infections written by David S. Hui and published by European Respiratory Society. This book was released on 2016-06-01 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral respiratory tract infections are important and common causes of morbidity and mortality worldwide. In the past two decades, several novel viral respiratory infections have emerged with epidemic potential that threaten global health security. This Monograph aims to provide an up-to-date and comprehensive overview of severe acute respiratory syndrome, Middle East respiratory syndrome and other viral respiratory infections, including seasonal influenza, avian influenza, respiratory syncytial virus and human rhinovirus, through six chapters written by authoritative experts from around the globe.
Book Synopsis Why Vaccines to HIV, HCV and Malaria Have So Far Failed - Challenges to Developing Vaccines against Immunoregulating Pathogens by : Shuo Li
Download or read book Why Vaccines to HIV, HCV and Malaria Have So Far Failed - Challenges to Developing Vaccines against Immunoregulating Pathogens written by Shuo Li and published by Frontiers Media SA. This book was released on 2016-09-14 with total page 159 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite continuous progress in the development of anti-viral and anti-bacterial/parasite drugs, the high cost of medicines and the potential for re-infection, especially in high risk groups, suggest that protective vaccines to some of the most dangerous persistent infections are still highly desirable. There are no vaccines available for HIV, HCV and Malaria, and all attempts to make a broadly effective vaccine have failed so far. In this Research Topic we look into why vaccines have failed over the years, and what we have learn from these attempts. Rather than only showing positive results, this issue aims to reflect on failed efforts in vaccine development. Coming to understand our limitations will have theoretical and practical implications for the future development of vaccines to these major global disease burdens.
Book Synopsis AIDS Research and Reference Reagent Program by :
Download or read book AIDS Research and Reference Reagent Program written by and published by . This book was released on 1989 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt:
