HIV Antigens Can Induce TGF-β1-Producing Immunoregulatory CD8+ T Cells

Abstract

HIV-infected individuals may progressively lose both HIV-specific and unrelated CTL responses despite the high number of circulating CD8+ T cells. In this study, we report that approximately 25% of HIV+ donors produced TGF-beta(1) in response to stimulation with HIV proteins or peptides. The production of TGF-beta(1) was sufficient to significantly reduce the IFN-gamma response of CD8+ cells to both HIV and vaccinia virus proteins. Ab to TGF-beta reversed the suppression. We found the source of the TGF-beta(1) to be predominantly CD8+ cells. Different peptide pools stimulated TGF-beta(1) and IFN-gamma in the same individual. The TGF-beta(1) secreting cells have distinct peptide specificity from the IFN-gamma producing cells. This represents an important mechanism by which an HIV-specific response can nonspecifically suppress both HIV-specific and unrelated immune responses.

The characterization and role of regulatory T cells in immune reactions

“…Another type of Tr1 cells (called CD8+ Tr1-like cells) has been also described. These cells also display regulatory properties exerted by IL-10 and can be generated by stimulation of naïve T CD8+ lymphocytes with IL-10-modulated myeloid DCs or activated plasmacytoid DCs (73,74,75). However, their precise role needs to be established.…”

TGF-β signaling in T cells: roles in lymphoid and epithelial neoplasia

“…TGF-b has been widely viewed as playing an important role in the biology of regulatory T cells, which have broadly been defined by their capacity to suppress immune responses, and each have been implicated in the induction of oral tolerance (Miller et al, 1992), suppression of autoimmune disease (Chrobak, 2003), susceptibility to infection (Garba et al, 2002;Kullberg et al, 2002;Monteleone et al, 2004), and cancerassociated immunosuppression (Fu et al, 2000). Various T-cell subsets, including CD4 þ , CD8 þ , and NK cells, have been shown to exert suppressor activity in different contexts, but it is the naturally occurring CD4 þ CD25 þ T cell that has emerged as the most well characterized (Shevach et al, 2001), and there has been an intense focus on the role of TGF-b in their development (Yamagiwa et al, 2001;Wan and Flavell, 2005), maintenance (Marie et al, 2005), and effector function (Piccirillo et al, 2002) (Figure 3).…”

Liver transplantation in human immunodeficiency virus-positive patients

“…An HCV infection is more likely to result in a chronic infection because of a weaker adaptive immune response and a reduced interferon-c response of CD8 þ cells. 22,23 In addition, the reduced CD4 þ /CD8 þ ratio that is associated with HIV infections also contributes because CD8 þ cells are more fibrogenic than CD4 þ cells. 24 Decreased interleukin-10 expression by intrahepatic CD4 þ cells also potentiates the profibrotic state.…”