CD8+ T suppressor lymphocytes have been described. However, the regulatory role of IL-10+ CD8+ Ts in modulating HIV-specific T cell responses remains unknown.
The aims proposed in this research plan contain a series of experiments designed to explore the role of HIV-specific IL-10+ CD8+ T cells in mediating T cell immune dysfunction in HIV infection. I hypothesize that HIV-specific IL-10+ CD8+ T cells exert an inhibitory effect on distinct populations of HIV-specific effector T cells.
Aim 1 explores the mechanisms of suppression utilized by the IL-10+ CD8+ Ts during HIV infection. The role of 1) contact dependent suppression, 2) cytokines such as IL-10 and TGF-beta, will be examined.
Aim 2 investigates the phenotypic characteristics and specificity of the IL-10+ CD8+ Ts during HIV infection.
This aim will focus on examining the suppressive effect of the IL-10+ CD8+ Ts to different HIV, and non-HIV-specific effector T cells. The expression by the IL- 10+ CD8+ Ts of various markers associated with regulatory T cells, such as CD25, FoxpS, CTLA-4 will also be assessed. ? ? ?
| Peña, José; Jones, Norman G; Bousheri, Stephanie et al. (2014) Lymphocyte activation gene-3 expression defines a discrete subset of HIV-specific CD8+ T cells that is associated with lower viral load. AIDS Res Hum Retroviruses 30:535-41 |
| Elrefaei, Mohamed; Burke, Candace M; Baker, Chris A R et al. (2010) HIV-specific TGF-beta-positive CD4+ T cells do not express regulatory surface markers and are regulated by CTLA-4. AIDS Res Hum Retroviruses 26:329-37 |
| Elrefaei, Mohamed; Burke, Candace M; Baker, Chris A R et al. (2009) TGF-beta and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells. PLoS One 4:e8194 |
| Elrefaei, Mohamed; Baker, Chris A R; Jones, Norman G et al. (2008) Presence of suppressor HIV-specific CD8+ T cells is associated with increased PD-1 expression on effector CD8+ T cells. J Immunol 180:7757-63 |
