Tissue resident memory T cells trigger rapid exudation and local antibody accumulation

Adaptive immunity is didactically partitioned into humoral and cell-mediated effector mechanisms, which may imply that each arm is separate and does not function together. Here, we report that the activation of CD8+ resident memory T cells in nonlymphoid tissues triggers vascular permeability, which facilitates rapid distribution of serum antibodies into local tissues. TRM reactivation was associated with transcriptional upregulation of antiviral signaling pathways as well as Fc receptors and components of the complement cascade. Effects were local, but evidence is presented that TRM in brain and reproductive mucosa are both competent to induce rapid antibody exudation. TRM reactivation in the mouse female genital tract increased local concentrations of virus-specific neutralizing antibodies including anti-vesicular stomatitis virus and passively transferred anti-HIV antibodies. We showed that this response was sufficient to increase the efficacy of ex vivo vesicular stomatitis virus neutralization. These results indicate that CD8+ TRM antigen recognition can enhance local humoral immunity. Microarray data comparing RNA isolated from murine female reproductive tract tissue from control tissue (SIIN) versus tissues where resident memory T cells were reactivated 9 hours prior (GP33). Control mice (SIIN) received the irrelevant peptide SIINFEKL transcervically. Experimental mice (GP33) recieved the peptide gp33, which P14 resident memory T cells specifically recognize, transcervically. female reproductive tract tissue from 3 mice per condition (control and Trm reactivated) were processed for total RNA 9 hours following treatment