Divergent behavior of mucosal memory T cells

Abstract

Memory CD4 T cells are strategically positioned at mucosal surfaces to initiate a robust adaptive immune response. The detection of specific antigen via the T-cell receptor causes these memory T cells to unleash a potent antimicrobial response that includes rousing local innate immune populations for tissue-specific defense. Paradoxically, these same memory T cells can also be stimulated by nonantigen-specific signals that are generated by the activity of local innate immune cells. This versatility of mucosal memory T cells in both the initiation and the sensing of local innate immunity could be a vitally important asset during pathogen defense but alternatively could be responsible for initiating and maintaining chronic inflammation in sensitive mucosal tissues.

Figure 1. Innate stimulation of T cells in mucosal tissues

Local innate immune activation or tissue stress can initiate a cytokine milieu capable of stimulating nearby memory T cells in the absence of TCR ligation. The synergy of IL-15 and TL1a in the presence of IL-12, IL-18 can increase expression of multiple pro-inflammatory cytokines from memory T cells. Such innate stimulation of CD4 and CD8 T cells has been observed in bacterial infection models in which IL-18R signaling contributes to the production of IFN-γ and host protection against pathogenic bacteria (Right). This non-cognate pathway might be particularly for the host if a pathogen evades antigen presentation or if a co-infection is present. However, innate stimulation of memory T cells in mucosal tissues might also induce or perpetuate harmful inflammatory responses (Left).