Co-Ordination of Mucosal B Cell and CD8 T Cell Memory by Tissue-Resident CD4 Helper T Cells

Abstract

Adaptive cellular immunity plays a major role in clearing microbial invasion of mucosal tissues in mammals. Following the clearance of primary pathogens, memory lymphocytes are established both systemically and locally at pathogen entry sites. Recently, resident memory CD8 T and B cells (T_RM and B_RM respectively), which are parked mainly in non-lymphoid mucosal tissues, were characterized and demonstrated to be essential for protection against secondary microbial invasion. Here we reviewed the current understanding of the cellular and molecular cues regulating CD8 T_RM and B_RM development, maintenance and function. We focused particularly on elucidating the role of a novel tissue-resident helper T (T_RH) cell population in assisting T_RM and B_RM responses in the respiratory mucosa following viral infection. Finally, we argue that the promotion of T_RH responses by future mucosal vaccines would be key to the development of successful universal influenza or coronavirus vaccines, providing long-lasting immunity against a broad spectrum of viral strains.

Keywords: mucosal immunity; non-lymphoid tissues; tissue resident memory B; tissue resident memory T.

Figure 1

Help of B cell immunity by T_RH or T_FH cells. Activated CD4 T cells migrate into the B cell zone to become mature CXCR5^hi T_FH cells to help B cells via CD40-CD40L, ICOS-ICOS-L interactions and cytokines including IL-21. T_RH precursors, which express low levels of CXCR5, can infiltrate into non-lymphoid tissues such as the lung. T_RH precursors adapt to the lung environment to become mature T_RH cells, thereby assisting B cell immunity in situ through the expression of CD40L.

Figure 2

T_RH cell help to CD8 T_RM cells. T_RH cells, which localize within the iBALT, secrete IL-21. Influenza NP_366–374-specific CD8 T_RM cells are located outside but near the border of iBALT structure and express high levels of IL-21 receptor. IL-21 secreted from T_RH cells promotes the expression of Blimp-1 (Prdm1), BATF and other molecules in CD8 T_RM cells, thereby maintaining NP_366–374-specific T_RM cell retention and survival in the lung.