Microbial infection primes a CD8+ cytotoxic T cell response that gives rise to a long-lived population of circulating memory cells able to provide protection against systemic reinfection. Despite this, effective CD8+ T cell surveillance of barrier tissues such as skin and mucosa typically wanes with time, resulting in limited T cell-mediated protection in these peripheral tissues. However, recent evidence suggests that a specialized subset of CD103+ memory T cells can permanently lodge and persist in peripheral tissues, and that these cells can compensate for the loss of peripheral immune surveillance by circulating memory T cells. Importantly, we have recently shown that these tissue-resident memory T cells (TRM) can be exploited in vaccination-like settings to provide superior protection from de novo virus infection in skin and vaginal mucosa. Our current work aims at identifying factors involved in the lodgment and long-term persistence of TRM cells in peripheral tissues. We are analyzing the TRM-precursor potential of different subtypes of effector and memory CD8+ T cells, and are defining the role of adhesion and migration receptors involved in TRM differentiation by these cells. Furthermore, we are testing the role of locally produced cytokines for their long-term survival in different organs. Such insights will guide and support the development of future vaccines targeting TRM cells at body surfaces for enhanced local immunity against peripherally invading pathogens.
Contact author: Laura Mackay – lkmackay@unimelb.edu.au