The Chemokine Receptor CXCR3 Promotes CD8+ T Cell Accumulation in Uninfected Salivary Glands but Is Not Necessary after Murine Cytomegalovirus Infection

Recent work indicates that salivary glands are able to constitutively recruit CD8 + T cells and retain them as tissue-resident memory T cells, independently of local infection, inflammation, or Ag. To understand the mechanisms supporting T cell recruitment to the salivary gland, we compared T cell migration to the salivary gland in mice that were infected or not with murine CMV (MCMV), a herpesvirus that infects the salivary gland and promotes the accumulation of salivary gland tissue-resident memory T cells. We found that acute MCMV infection increased rapid T cell recruitment to the salivary gland but that equal numbers of activated CD8 + T cells eventually accumulated in infected and uninfected glands. T cell recruitment to uninfected salivary glands depended on chemokines and the integrin α 4 . Several chemokines were expressed in the salivary glands of infected and uninfected mice, and many of these could promote the migration of MCMV-specific T cells in vitro. MCMV infection increased the expression of chemokines that interact with the receptors CXCR3 and CCR5, but neither receptor was needed for T cell recruitment to the salivary gland during MCMV infection. Unexpectedly, however, the chemokine receptor CXCR3 was critical for T cell accumulation in uninfected salivary glands. Together, these data suggest that CXCR3 and the integrin α 4 mediate T cell recruitment to uninfected salivary glands but that redundant mechanisms mediate T cell recruitment after MCMV infection.