CD4+ T cells regulate skin resident memory CD8+ T cells (TRM) (49.8)

Abstract

Abstract The requirement of CD4+ T cell help for CD8+ T cell responses has been extensively explored in secondary lymphoid organs using systemic infection models. Whether such help also exists in peripheral tissues like the skin is unknown. We recently reported that skin resident memory CD8+ T cells (TRM) are non-recirculating and are superior to central memory CD8+ T cells (TCM) in protecting against re-infection. Interestingly, we also found that the acute CD8+ T cell migration into infected skin does not require CD4+ T cell help. Further study showed that the acute protection response of CD8+ T cells in the skin was equivalent in wild type and CD4-deficient mice. We next asked the role of CD4+ T cells in CD8+ TRM protective responses in the skin. To our surprise, the absence of CD4+ T cells did not impair the survival of CD8+ TRM in the skin. However, the recall response of CD8+ TRM in previously infected skin was significantly compromised in CD4-/- mice. The viral load assay further showed that the recall response of CD8+ TRM was significantly compromised when memory CD4+ T cells in the skin were depleted, suggesting that signals from memory CD4+ T cells in the skin are delivered to CD8+ TRM locally. Taken together, these data imply that while CD4+ T cells are not required both for acute CD8+ T cell response and maintenance CD8+ TRM in the skin, they do play an important role in regulating recall responses of CD8+ TRM.