Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state

摘要

( ) Definition of MP cells. The representative dot plot shows CD44 and CD62L expression by Foxp3 CD4 αβT lymphocytes in spleen from five mice. ( and ) T-bet and RORγt expression in MP and naïve CD4 T lymphocytes. The representative plots show ( ) T-bet-AmCyan and RORγt-E2Crimson expression in the indicated cell populations obtained from three T-bet-AmCyan RORγt-E2Crimson double reporter mice and ( ) T-bet and CXCR3 protein levels in the same populations from five mice. ( – ) T-bet MP cells produce IFN-γ in the absence of TCR signaling in infected mice. Experimental design. CD4CreERT2 TCRα IFN-γ-YFP T-bet-AmCyan mice receiving TMX on Days -10 and -8 were infected with on Day 0 and splenocytes measured for IFN-γ-YFP expression in T-bet , T-bet , and T-bet TCRβ MP subsets several days later. TCRβ expression in MP cells and T-bet-AmCyan levels in their TCRβ fraction on Day 0. IFN-γ-YFP expression in T-bet , T-bet , and T-bet TCRβ MP cells on Days 0, 2, and 8 following infection. A representative histogram is shown (orange, purple, and red lines indicate YFP expression by T-bet TCRβ MP cells on Days 0, 2, and 8, respectively) while the graph depicts the MFI (mean ± SD) of IFN-γ-YFP expression in the indicated populations (red T-bet TCRβ MP; green T-bet TCRβ MP; blue T-bet TCRβ MP; gray TCRβ Naïve; Day 0  = 6 mice; Day 2  = 3 mice; Day 8  = 3 mice). Data are representative of two independent experiments performed. ( and ) T-bet MP cells can prolong survival in infection. Experimental design. DKO mice were infected with on Day 0, received sorted T-bet , T-bet , or T-bet MP cells on the next day, and were monitored for survival. Survival of -infected DKO mice that received each MP subset (red, green, and blue lines show T-bet , T-bet , and T-bet MP cells, respectively; T-bet MP  = 5 mice; T-bet MP  = 5 mice; T-bet MP  = 5 mice; Untransferred controls  = 9 mice). Data are pooled from two experiments performed. ( ) A two-sided and ( ) a log-rank tests were performed to assess significance. Source data are provided as a Source Data file.