Discipline in Stages: Regulating CD8+ Resident Memory T Cells

Abstract

Resident memory CD8+ T (TRM) cells are a lymphocyte lineage distinct from circulating memory CD8+ T cells. TRM lodge within peripheral tissues and secondary lymphoid organs where they provide rapid, local protection from pathogens and control tumor growth. However, dysregulation of CD8+ TRM formation and/or activation may contribute to the pathogenesis of autoimmune diseases. Intrinsic mechanisms, including transcriptional networks and inhibitory checkpoint receptors control TRM differentiation and response. Additionally, extrinsic stimuli such as cytokines, cognate antigen, fatty acids, and damage signals regulate TRM formation, maintenance, and expansion. In this review, we will summarize knowledge of CD8+ TRM generation and highlight mechanisms that regulate the persistence and responses of heterogeneous TRM populations in different tissues and distinct microenvironments.

Intestinal CD8+ tissue‐resident memory T cells: From generation to function

“…A crucial role for TGF-β in tissue retention of Trm has been shown in multiple tissues, including skin and gut [31,51,60]. In fact, TGF-β signaling induces CD103 expression and promotes Trm maintenance across organs [43]. Zhang et al reported two distinct functions for TGF-β signaling during the formation and maintenance of intestinal Trm in a model of systemic infection with the LCMV strains Armstrong (Arm) and Clone 13, which promote acute and chronic infection, respectively.…”

“…CD49a (Integrin β1, or very late antigen 1 (VLA1)), a subunit of the collagen receptor α1β1, is also well‐known to favor Trm maintenance in epithelial tissues such as the skin by binding to type I and IV‐ collagen [ 43 ], and was found to be up‐regulated in human gut Trm [ 44 ] and necessary for maintenance of Trm in the SI epithelium in mice [ 45 ].…”

“…A crucial role for TGF‐β in tissue retention of Trm has been shown in multiple tissues, including skin and gut [ 31 , 51 , 60 ]. In fact, TGF‐β signaling induces CD103 expression and promotes Trm maintenance across organs [ 43 ]. Zhang et al.…”

“…The protective potential of intestinal Trm has been suggested by several studies, although the evidence appears less robust than for T cells residing at other anatomical locations, such as the skin, possibly due to the inherent difficulties in isolating the relative impact of these cells from the contribution of circulating cells [ 43 ].…”

The Emerging Role of Tissue-Resident Memory CD8+ T Lymphocytes in Human Digestive Tract Cancers

“…CD8 + Trm cells mainly reside on the barrier epithelium of nonlymphoid organs and respond rapidly to both viral and bacterial infection and tumorigenesis. In human digestive tract mucosa, CD8 + Trm cells play a key role in anti-infection and antitumor immunity because they elicit a rapid immune response after antigen stimulation (7) .…”