HIV-Specific IL-10-Positive CD8+ T Cells Suppress Cytolysis and IL-2 Production by CD8+ T Cells

Abstract

IL-10 producing T cells inhibit Ag-specific CD8+ T cell responses and may play a role in the immune dysregulation observed in HIV infection. We have previously observed the presence of HIV-specific IL-10-positive CD8+ T cells in advanced HIV disease. In this study, we examined the suppressive function of the Gag-specific IL-10-positive CD8+ T cells. Removal of these IL-10-positive CD8+ T cells resulted in increased cytolysis and IL-2, but not IFN-γ, production by both HIV- and human CMV-specific CD8+ T cells. In addition, these IL-10-positive CD8+ T cells mediated suppression through direct cell-cell contact, and had a distinct immunophenotypic profile compared with other regulatory T cells. We describe a new suppressor CD8+ T cell population in advanced HIV infection that may contribute to the immune dysfunction observed in HIV infection.

HIV-Specific TGF-β-Positive CD4+T Cells Do Not Express Regulatory Surface Markers and Are Regulated by CTLA-4

“…IL-10-producing HIV-specific CD4 þ Treg suppress HIV-specific T cell function in vitro, 46,47 and their detection is associated with progressive HIV disease. 10,37,48,49 We found no significant IL-10 production by the HIV-specific TGF-b-positive CD4 þ T cells in our study. We proposed that the concomitant presence of suppressor IL-10-positive CD8 þ T cells and HIV-specific TGF-b-positive CD4 þ T cells may promote additive suppression of HIV-specific T cell responses.…”

“…1,2 These CD4 þ Treg express high levels of FOXP3 and CD25 [3][4][5][6] and low surface expression of CD127. 7,8 CD4 þ Treg cells exert their inhibitory effects on T cell proliferation and cytokine production through a cell-cell contact-dependent mechanism 4,[9][10][11] and the secretion of immunosuppressive cytokines such as interleukin (IL)-10 and transforming growth factor b (TGF)-b. 12,13 Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is constitutively expressed on CD4…”

“…10,33 Demographic information and CD4 þ T cell count were obtained at the time of enrollment and blood draw. Institutional Review Board approvals were obtained from the California Department of Public Health and UCSF Committee on Human Research, and all study participants gave written informed consent.…”

“…10 Briefly, PBMCs ( 1Â10 6 ) were incubated with HIV peptide pools for 12-14 h as described above for intracellular cytokine staining. Cells were then stained with an amine reactive viability dye as a dead cell exclusion marker (Molecular probes) 36 and the following antibodies: FOXP3 FITC (eBioscience), TGF-b PE, CD4 PerCP Cy5.5, CD8 PE CY7, CD25 allophycocyanin, and CD3 AmCyan (BD Pharmingen).…”

HIV induced suppression of host immunity: relevance to <i>Mycobacterium tuberculosis</i> infections

“…Eventual loss of CD4+ T cells [38], elevated levels of suppressor of cytokine signalling (SOCS-1) [39], decreased IL-12p40 [40], elevated levels of IL-10 [41,42], decreased IFNs mediated response [43][44][45] etc., were observed among infected individuals. In turn, the loss of potent CD4+ T cells driven immune response, favors the reactivation of latent TB infection [46,47].…”