While animal model studies point to the importance of CD8 T cell responses in controlling HIV-1 replication, the specific quality of these cells achieving this control are unknown. Numerous studies have attempted to correlate different parameters of HIV-1 specific CD8 T cells with clinical markers of disease progression; however, inconsistent data has been attained. Also, for the studies that have seen correlations with plasma viral load, it is unclear whether the observed CD8 T cells parameter are just the result of low viral replication rather than a causative factor in controlling this replication. The problem stems from the fact that most assays do not measure the actual function of CD8 T cells in controlling HIV-1 but instead measure potential surrogate markers of this control.
Specific Aim 1 of our proposal will analyze the efficiency of HIV-1 CD8 T cell clones in killing and suppressing HIV-1 replication using in vitro viral assays. Every clone will be identified on the basis T cell receptor ? gene (TCRB) sequencing. Using polychromatic flow cytometry in specific aim 2, we will sort HIV-1 specific CD8 T cells according to their capacity to express combinations of 4 different functional parameters (IFN-?, IL-2, TNF-a, and CD107). We will then determine which of the specific populations of HIV-1 CD8 T cells is enriched with clones that efficiently control virus in vitro. Our findings will have important implications fro HIV immunopathogenesis and vaccine design by supplying an HIV-1 specific CD8 T cell phenotype that results in efficient HIV-1 control. ? ? ?
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| Akinsiku, Olusimidele T; Bansal, Anju; Sabbaj, Steffanie et al. (2011) Interleukin-2 production by polyfunctional HIV-1-specific CD8 T cells is associated with enhanced viral suppression. J Acquir Immune Defic Syndr 58:132-40 |
| Williams, LaTonya D; Bansal, Anju; Sabbaj, Steffanie et al. (2011) Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers. J Virol 85:2316-24 |
| Bansal, Anju; Carlson, Jonathan; Yan, Jiyu et al. (2010) CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription. J Exp Med 207:51-9 |
| Bansal, Anju; Yue, Ling; Conway, Joan et al. (2007) Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents. AIDS 21:2387-97 |
