Mechanisms regulating expansion of CD8+ T cells during HIV ‐1 infection

Abstract Abnormal immune activation and expansion of CD8+ T cells, especially of memory and effector phenotypes, take place during HIV‐1 infection, and these abnormal features persist during administration of antiretroviral therapy (ART) to infected patients. The molecular mechanisms for CD8+ T‐cell expansion remain poorly characterized. In this article, we review the literature addressing features of CD8+ T‐cell immune pathology and present an integrated view on the mechanisms leading to abnormal CD8+ T‐cell expansion during HIV‐1 infection. The expression of molecules important for directing the homing of CD8+ T cells between the circulation and lymphoid tissues, in particular CCR5 and CXCR3, is increased in CD8+ T cells in circulation and in inflamed tissues during HIV‐1 infection; these disturbances in the homing capacity of CD8+ T cells have been linked to increased CD8+ T‐cell proliferation. The production of IL‐15, a cytokine responsible for physiological proliferation of CD8+ T cells, is increased in lymphoid tissues during HIV‐1 infection as result of microbial translocation and severe inflammation. IL‐15, and additional inflammatory cytokines, may lead to deregulated proliferation of CD8+ T cells and explain the accumulation of CD8+ T cells in circulation. The decreased capacity of CD8+ T cells to localize to gut‐associated lymphoid tissue also contributes to the accumulation of these cells in blood. Control of inflammation, through ART adminis...
Source: Journal of Internal Medicine - Category: Internal Medicine Authors: Tags: Review Source Type: research