Interrogating the MHC and Cytokine Requirements for CD4+CD8aa+ Intestinal Intraepithelial T cells

Authors

• DJ Lanasa
• C Li
• JH Park

Abstract

Gut immunity is maintained by a diverse array of intraepithelial lymphocytes (IELs) among which alpha beta T cells that co-express the coreceptors CD4 and CD8aa have emerged as critical players. CD4+CD8aa+ double-positive (DP) IELs exhibit mixed functional and phenotypic features of both CD4 helper and CD8 cytotoxic T cells, and are considered to occupy a unique niche in maintaining intestinal barrier immunity. While DP IELs are known to be derived from conventional CD4 T cells which are MHC-II dependent, whether MHC-I molecules that interact with CD8aa also contribute to the differentiation and maintenance of DP IELs remains incompletely known. By using a series of genetically engineered mouse models, here, we demonstrate a previously unappreciated effect of non-classical MHC-I molecules in the generation of DP IELs. Moreover, DP IELs were dramatically reduced in Interferon-gamma-deficient mice, a mouse model with impaired MHC-I and MHC-II expression in the intestine. These results suggested a critical role for cytokines in DP IEL generation, and we affirmed this notion in mice deficient for the homeostatic cytokines IL-7 or IL-15. Notably, IL-7 and IL-15 signaling inhibited the generation of DP IELs by activating STAT5 signaling. Collectively, these data demonstrate a unique requirement of DP IEL generation and maintenance with the cooperation of multiple factors, expanding the current understanding to provide new insights on the MHC and cytokine requirements of DP IELs.

Scientific Focus Area: Immunology

This page was last updated on Tuesday, August 6, 2024