Characteristics of CD8⁺ and CD4⁺ Tissue-Resident Memory Lymphocytes in the Gastrointestinal Tract

Figure 2

Functions of GI-TRMs. (a) GI-TRMs are capable of providing the front-line defenses against pathogens at the most vulnerable entry port. (b) CD4⁺ TRMs are retained in the tissues and can be reactivated locally following reinfection. CD4⁺ TRMs are expanded and can become effector Th1, Th17, or Th2-type cells that mediate rapid clearance of the infection. (c) Small intestine lamina propria Tregs are differentiated into all three subtypes based on the expression of RORγt (Rorc), GATA3, and Helios: RORγt^–Helios^– Tregs primarily generated in response to dietary macromolecules and are proposed to be helpful in containing childhood allergies. GATA3⁺Helios⁺ Tregs expressed ST2 receptor that interacts with tissue damage-induced alarmin IL-33 to tissue repair. RORγt⁺Helios^– Tregs were involved in establishing tolerance towards local microbes. (d) Upon antigen resensitization or CRC, CD8⁺ TRMs could express NK receptors (e.g., CD94 and NKG2D), exerting a NK-like function as well as producing granzyme B and inflammatory cytokines. (e) GI-TRMs employed myriad mechanisms for CRC clearance such as constitutively expressed granzyme B, IFNγ, perforin, and IL-2 and played a cytotoxic role. Meanwhile, GI-TRMs recruited circulating memory CD8⁺ T cells, B cells, and other lymphocytes to the sites of tumor.