CX3CR1/Fractalkine receptor expression separates memory CD8+ T cells with distinct functional profiles (RNA-seq)

Memory T cells are important for protective immunity against infectious microorganisms. Such protection is achieved by cooperative action of memory T cell populations that differ in their tissue localization and functionality. We report on the identification of the fractalkine receptor CX3CR1 as marker for stratification of memory T cells with cytotoxic effector function from those with proliferative function in both, mice and man. Based on CX3CR1 and CD62L expression levels four distinct memory T cell populations can be distinguished based on their functional properties. Transcriptome and proteome profiling revealed that CX3CR1 expression was superior to CD62L to resolve memory T cell functionality and allowed determination of a core signature of memory T cells with cytotoxic effector function. This identifies a CD62Lhi CX3CR1+ memory T cell population with an identical gene signature to CD62LlowCX3CR1+ effector memory T cells. In lymph nodes, this so far unrecognized CD62LhiCX3CR1+ T cell population shows a distinct migration pattern and anatomic positioning compared to CD62LhiCX3CR1neg TCM. Furthermore, CX3CR1+ memory T cells were scarce or absent during chronic HBV, HCV and HIV infection in man and chronic LCMV infection in mice confirming the value of CX3CR1+ in understanding principles of protective immune memory. Overall design: CD8+ T cells were isolated and directly assessed. After harvesting, cells were immediately lysed in Trizol (Invitrogen) before storage at -80°C for RNA isolation.

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Böttcher JP, Beyer M, Meissner F, Abdullah Z, Sander J, Höchst B, Eickhoff S, Rieckmann JC, Russo C, Bauer T, Flecken T, Giesen D, Engel D, Jung S, Busch DH, Protzer U, Thimme R, Mann M, Kurts C, Schultze JL, Kastenmüller W, Knolle PA