CXCL17 Chemokine-Dependent Mobilization of Memory CXCR8+CD8+ TEM and TRM Cells in the Vaginal Mucosa is Associated with Protection Against Genital Herpes

摘要

Circulating conventional memory CD8⁺ T cells (i.e. the effector memory (CD8⁺ TEM) and the central memory (CD8⁺ TCM) subsets) and non-circulating tissue-resident memory CD8⁺ T cell subset (CD8⁺ TRM) play a critical role in mucosal immunity. Mucosal chemokines, including the recently discovered CXCL17, are also important in mucosal immunity because they are homeostatically expressed in mucosal tissues. However, whether the CXCL17 chemokine contributes to the mobilization of memory CD8⁺ T cell subsets, to access infected mucosal tissues remains to be elucidated. Herein, we report that after intravaginal herpes simplex type 1 (HSV-1) infection of B6 mice, we detected high expression levels of CXCL17 and increased numbers of CD44^highCD62^LowCD8⁺ TEM and CD103^highCD8⁺ TRM cells, expressing CXCR8, the cognate receptor of CXCL17, in the vaginal mucosa (VM) of mice with reduced genital herpes infection and disease. In contrast to wild type B6 mice, the CXCL17^−/− deficient mice developed: (i) fewer CXCR8⁺CD8⁺ TEM and TRM cells associated with more virus replication in the VM and more latency established in dorsal root ganglia (DRG); (ii) reduced numbers and frequencies of functional CD8⁺ T cells in the VM. These findings suggest that the CXCL17/CXCR8 chemokine pathway play a crucial role in mucosal vaginal immunity by promoting the mobilization of functional protective CD8⁺ TEM and CD8⁺ TRM cells, within this site of acute and recurrent herpes infection.