Murine CMV Infection Induces the Continuous Production of Mucosal Resident T Cells

• MCMV induces resident memory CD8s in multiple mucosal tissues early after infection
• TRM maintenance and IEL localization in the salivary gland does not depend on CD103
• MCMV-specific CD8s circulating during latency have reduced capacity to form new TRM
• Antigen promotes the late recruitment and formation of TRM in the salivary gland

SummaryCytomegalovirus (CMV) is a herpesvirus that persists for life and maintains extremely large numbers of T cells with select specificities in circulation. However, it is unknown how viral persistence impacts T cell populations in mucosal sites. We found that many murine (M)CMV-specific CD8s in mucosal tissues became resident memory T cells (TRM). These cells adopted an intraepithelial localization in the salivary gland that correlated with, but did not depend on, expression of the integrin CD103. MCMV-specific TRM cells formed early after infection, and spleen-localized cells had reduced capacities to become TRM at late times. Surprisingly, however, small numbers of new TRM cells were formed from the circulating pool throughout infection, favoring populations maintained at high levels in the blood and shifting the immunodominance within the TRM populations over time. These data show that mucosal TRM populations can be dynamically maintained by a persistent infection.

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