Journal
JOURNAL OF INTERNAL MEDICINE
Volume 283, Issue 3, Pages 257-267Publisher
WILEY
DOI: 10.1111/joim.12722
Keywords
CD8+T cells; chemokines; homing; IL-15; inflammation
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Funding
- Karolinska Institutet
- Swedish Medical Research Council
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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 administration during primary HIV-1 infection or therapies aimed at controlling inflammation during HIV-1 infection, is pivotal to prevent abnormal expansion of CD8+ T cells during HIV-1 infection.
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