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Impaired IFN-γ Production by Viral Immunodominant Peptide-specific Tetramer+ CD8+ T Cells in HIV-1 Infected Patients is not Secondary to HAART

By Nattawat Onlamoon, Kovit Pattanapanyasat and Aftab A. Ansari


Studies on PBMC samples from HIV-1 infected patients have shown that despite substantial number of HIV specific CTLs, these patients gradually progress to AIDS. The present study was conducted to determine whether this paradox was secondary to the influence of protease inhibitors being utilized by these patients. Thus, aliquots of PBMC samples from 10 HIV infected humans with no prior history of anti-retroviral drug therapy (ART) and 6 HIV-infected patients that had been on HAART for >1 year were analyzed for the frequency of HIV-1 Nef and Gag dominant peptide specific tetramer+ cells, respectively. The tetramer+ PBMCs were analyzed for their ability to synthesize specific peptide induced IFN-γ utilizing both the ELISPOT and the intracellular cytokine (ICC) assays. Results of the studies showed that there was an overall correlation between the frequency of Nef and Gag peptide tetramer+ cells and the frequency of IFN-γ synthesizing cells as assayed by either ICC or ELISPOT assay, markedly reduced values of IFN-γ synthesizing cells per unit tetramer+ cells were noted in both group of patients. These data suggest that the frequency of HIV-specific CD8+T cells is maintained during the chronic phase of infection, their ability to function is compromised and is not a reflection of ART. While the addition of IL-2, anti-CD40L and allogeneic cells led to partial increase in the ability of the tetramer+ cells to synthesize IFN-γ, the addition of IL-4, IL-12, anti-CD28 or a cocktail of anti-TGF-β, TNF-α and IL-10 failed to augment the IFN-γ response

Topics: Research Article
Publisher: Hindawi Publishing Corporation
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    1. (2000). A significant number of human immunodeficiency virus epitope-specific cytotoxic T lymphocytes detected by tetramer binding do not produce gamma interferon”,
    2. (1998). An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses”,
    3. (1995). Anti-HIV type 1 cytotoxic T lymphocyte effector activity and disease progression in the first 8 years of HIV type 1 infection of homosexual men”,
    4. (2000). Anti-human immunodeficiency virus type 1 (HIV-1) CD8(þ) T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency”,
    5. (2001). Assessing CD8 T cell number and dysfunction in the presence of antigen”,
    6. (1999). Association between virusspecific cytotoxic T-lymphocyte and helper responses in human immunodeficiency virus type 1 infection”,
    7. (2001). CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection”,
    8. (2001). Control of T-cell activation by CD4þ CD25þ suppressor T cells”,
    9. (1999). Control of viremia in simian immunodeficiency virus infection by CD8þ lymphocytes”,
    10. (1997). Cytotoxic T cells and viral hepatitis”,
    11. (1996). Cytotoxic T lymphocytes in asymptomatic longterm nonprogressing HIV-1 infection. Breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load”,
    12. (2001). Detection of intracellular phosphorylated STAT-4 by flow cytometry”,
    13. (2001). Differential effects of HIV-1 protease inhibitors on dendritic cell immunophenotype and function”,
    14. (1999). Dramatic rise in plasma viremia after CD8(þ) T cell depletion in simian immunodeficiency virus-infected macaques”,
    15. (2000). Functionally inert HIV-specific cytotoxic T lymphocytes do not play a major role in chronically infected adults and children”,
    16. (2001). High viral burden in the presence of major HIV-specific CD8(þ) T cell expansions: evidence forimpaired CTL effector function”,
    17. (2000). HIV-specific CD8(þ) T cells produce antiviral cytokines but are impaired in cytolytic function”,
    18. (1987). HIV-specific cytotoxic T lymphocytes in seropositive individuals”,
    19. (1995). HIV-specific cytotoxic T-cells in HIVexposed but uninfected Gambian women”,
    20. (2000). Human immunodeficiency virus type 1-and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(þ) T cells”,
    21. (2000). Human immunodeficiency virus-specific circulating CD8 T lymphocytes have down-modulated CD3zeta and CD28, key signaling molecules for T-cell activation”,
    22. (2000). Impaired function of circulating HIV-specific CD8(þ) T cells in chronic human immunodeficiency virus infection”,
    23. (1996). Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes”,
    24. (1995). Kinetics of Gag-specific cytotoxicT lymphocyte responses during the clinical courseof HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics”,
    25. (2001). Long-term protease inhibitor-containing therapy results in limited improvement in T cell function but not restoration of interleukin-12 production in pediatric patients with AIDS”,
    26. (2002). Persistent numbers of tetramer þ CD8(þ) T cells, but loss of interferon-gamma þ HIV-specific T cells during progression to AIDS”,
    27. (1996). Phenotypic analysis of antigen-specific T lymphocytes”,
    28. (2000). Putative immunodominant human immunodeficiency virus-specific CD8(þ) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype”,
    29. (1998). Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA”,
    30. (1993). Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein–Barr virus in late disease”,
    31. (1997). Rapid effector function in CD8þ memory T cells”,
    32. (2001). Reduction in CD8þ cell noncytotoxic antiHIV activity in individuals receiving highly active antiretroviral therapy during primary infection”,
    33. (1996). Resistance to HIV-1 infection among persistently seronegative prostitutes in
    34. (1992). Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones”,
    35. (1996). Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection”,
    36. (1994). Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome”,
    37. (1998). Viral immune evasion due to persistence of activated T cells without effector function”,
    38. (1994). Virus-specific CD8þ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection”,

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