Cutting Edge: Optimal Formation of Hepatic Tissue-Resident Memory CD4 T Cells Requires T-bet Regulation of CD18

J Immunol. 2023 Jul 15;211(2):180-185. doi: 10.4049/jimmunol.2300017.


CD4 tissue-resident memory T cells (TRMs) allow robust protection of barrier surfaces against pathogens. We investigated the role of T-bet in the formation of liver CD4 TRMs using mouse models. T-bet-deficient CD4 T cells did not efficiently form liver TRMs when compared with wild-type (WT). In addition, ectopic expression of T-bet enhanced the formation of liver CD4 TRMs, but only when in competition with WT CD4 T cells. Liver TRMs also expressed higher levels of CD18, which was T-bet dependent. The WT competitive advantage was blocked by Ab 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 TRMs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD18 Antigens
  • CD4-Positive T-Lymphocytes*
  • CD8-Positive T-Lymphocytes*
  • Immunologic Memory
  • Liver
  • Memory T Cells
  • Mice


  • CD18 Antigens