Optimal formation of Hepatic Tissue Resident Memory CD4 T cells Requires T-bet Regulation of CD18

• Published in: The Journal of immunology (1950) Vol. 211; no. 2; pp. 180 - 185
• Main Authors: Depew, Claire E., Nguyen, Alana T., Franke, Marissa C., Calderon, Jesica, Sciammas, Roger, McSorley, Stephen J.
• Format: Journal Article
• Language: English
• Published: 15-07-2023
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.2300017

Tissue resident memory (TRM) CD4 T cells allow robust protection of barrier surfaces against pathogens. We investigated the role of T-bet in the formation of liver CD4 TRM using mouse models. T-bet-deficient CD4 T cells did not efficiently form liver TRM when compared to wildtype. Additionally, ectopic expression of T-bet enhanced the formation of liver CD4 TRM, but only when in competition with wild-type CD4 T cells. Liver TRM also expressed higher levels of CD18 which was T-bet dependent. The wildtype competitive advantage was blocked by antibody neutralization of CD18. Taken together, our data show that activated CD4 T cells compete for entry to liver niches via T-bet-induced expression of CD18, allowing TRM precursors to access subsequent hepatic maturation signals. These findings uncover an essential role for T-bet in liver TRM CD4 formation and suggest targeted enhancement of this pathway could increase the efficacy of vaccines that require hepatic TRM.