A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells

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Science  28 Aug 2014:
DOI: 10.1126/science.1257530

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CD8 tissue resident T cells (TRM) provide efficient local control of viral infection, but the role of CD4 TRM is less clear. Here, by using parabiotic mice, we show that a preexisting pool of CD4 TRM cells in the genital mucosa was required for full protection from a lethal herpes simplex virus 2 (HSV-2) infection. Chemokines secreted by a local network of macrophages maintained vaginal CD4 TRM in memory lymphocyte clusters (MLCs), independently of circulating memory T cells . CD4 TRM within the MLC were enriched in clones that expanded in response to HSV-2. Our results highlight the need for vaccine strategies that enable establishment of TRM for protection from a sexually transmitted virus, and provide insights as to how such pool might be established.

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