Resident memory CD8 T cells trigger protective innate and adaptive immune responses

Abstract

The pathogen recognition theory dictates that upon viral infection, the innate immune system first detects microbial products, and then responds by providing instructions to adaptive CD8 T cells. Here, we show in mice that resident memory CD8 T cells (TRM), non-recirculating cells located at common sites of infection, can achieve near sterilizing immunity against viral infections by reversing this flow of information. Upon antigen re-sensitization within the mouse female reproductive mucosae, CD8+ TRM secrete cytokines that trigger rapid adaptive and innate immune responses including local humoral responses, maturation of local dendritic cells, and activation of natural killer cells. This provided near sterilizing immunity against an antigenically unrelated viral infection. Thus, CD8+ TRM rapidly trigger an antiviral state by amplifying receptor-derived signals from previously encountered pathogens.

Is adaptive-innate lymphocyte cross-talk driving mucosal disease?

“…(1) are consistent with the idea that signals derived from both innate and adaptive cells regulate the activation of innate lymphocytes in nonlymphoid tissues, and thereby contribute to mucosal inflammation and disease (6,7,9,12,15,16). This lymphocyte cross-talk is an intriguing model for the amplification of adaptive immunity and raises important mechanistic questions (further information is provided in refs.…”

“…It has been recently proposed that, in addition to their immediate effector function, T cells may act as local antigen-specific sensors that instruct other cells to orchestrate local immune responses, and thereby amplify their antigen-dependent effects (5,6). This "sensing and alarming" function includes the recruitment of additional immune cells, the activation of tissue-resident lymphocytes, and the activation of epithelial cells (5,7,8). Although such amplification is likely beneficial in the rapid response to invading pathogens, T cells reacting to environmental (e.g., food, commensal microbiota) or self-antigens may exacerbate or maintain inflammatory diseases also by coactivating innate lymphocytes (6).…”

Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract

“…CD8 + TRMs can be identified by the expression of CD69 and CD103, the αE portion of the αEβ7 integrin that allows interactions with E‐cadherin expressed on epithelial cells (Rosato, Beura & Masopust, 2017). CD103 + CD8 + T cells provide critical protection against viral infections due to privilege anatomical location within the epithelium, rapid local cytotoxic function, and induction of tissue antiviral state through the production of IFNγ and other pro‐inflammatory cytokines (Rosato et al., 2017; Schenkel et al., 2014). …”

Tissue-resident memory T cells live off the fat of the land

“…However, the direct interpretation of T rm cell antiviral function is confounded by their ability to potently recruit and synergize with circulating T cells to establish a protective microenvironment [9,10]. FTY720, a S1PR1 antagonist, is commonly used to inhibit T cell recruitment into tissues by blocking their egress from secondary lymphoid organs.…”