GITR Intrinsically Sustains Early Type 1 and Late Follicular Helper CD4 T Cell Accumulation to Control a Chronic Viral Infection

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The natural rodent pathogen LCMV clone 13 causes a persistent viral infection in mice and has successfully predicted several immunological factors that are relevant to human chronic viral infection such as HIV. LCMV clone 13 infection is ultimately controlled by cell-mediated and humoral immune responses by day 60–90 post-infection in CD4 T cell-sufficient mice. While it has been known for several years that CD4 T cell help is critical for control of LCMV clone 13, research to date has been largely limited to the regulatory factors that contribute to late CD4 T cell dysfunction, with little knowledge of the role of T cell co-stimulatory factors in sustaining CD4 T cells to help cell-mediated and humoral immune responses. Using GITR-deficient mice, we show that the co-stimulatory molecule GITR plays a critical cell-intrinsic role in early CD4 T cell accumulation to support cytotoxic T cell responses and late LCMV-specific IgG production. The early effects of Th1 on CTL responses are IL-2-dependent. Mice lacking GITR have up to 35-fold higher viral burden relative to GITR-sufficient controls. Taken together, we demonstrate a critical cell-intrinsic role for GITR is sustaining CD4 T cell responses to control chronic LCMV infection. Thus, GITR on CD4 T cells may critically contribute to the initial viral set-point in infections such as HIV.

Vyšlo v časopise: GITR Intrinsically Sustains Early Type 1 and Late Follicular Helper CD4 T Cell Accumulation to Control a Chronic Viral Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004517
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004517

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