biostudies-literatureKrueger PDNIAID NIH HHSNHLBI NIH HHSNIH687-701.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC8495663biostudies-literatureUnknown54(4)Interferon-γ (IFN-γ)-producing CD4⁺ T helper-1 (Th1) cells are critical for protection from microbes that infect the phagosomes of myeloid cells. Current understanding of Th1 cell differentiation is based largely on reductionist cell culture experiments. We assessed Th1 cell generation in vivo by studying antigen-specific CD4⁺ T cells during infection with the phagosomal pathogen Salmonella enterica (Se), or influenza A virus (IAV), for which CD4⁺ T cells are less important. Both microbes induced T follicular helper (Tfh) and interleukin-12 (IL-12)-independent Th1 cells. During Se infection, however, the Th1 cells subsequently outgrew the Tfh cells via an IL-12-dependent process and formed subsets with increased IFN-γ production, ZEB2-transcription factor-dImmunityTwo sequential activation modules control the differentiation of protective T helper-1 (Th1) cells.PMC8495663R01 AI103760T32 AI083196T32 HL007062R01 AI039614R01 AI027998T32 AI007313Osum KCDileepan TKrueger PDLanglois RAGoldberg MFHong SWKotov DIJenkins MKfalseTwo sequential activation modules control the differentiation of protective T helper-1 (Th1) cells.Interferon-γ (IFN-γ)-producing CD4⁺ T helper-1 (Th1) cells are critical for protection from microbes that infect the phagosomes of myeloid cells. Current understanding of Th1 cell differentiation is based largely on reductionist cell culture experiments. We assessed Th1 cell generation in vivo by studying antigen-specific CD4⁺ T cells during infection with the phagosomal pathogen Salmonella enterica (Se), or influenza A virus (IAV), for which CD4⁺ T cells are less important. Both microbes induced T follicular helper (Tfh) and interleukin-12 (IL-12)-independent Th1 cells. During Se infection, however, the Th1 cells subsequently outgrew the Tfh cells via an IL-12-dependent process and formed subsets with increased IFN-γ production, ZEB2-transcription factor-d2021-01-01T00:00:00Z2021 Apr2026-05-09T04:09:50.854Z2024-11-20T17:18:57.47ZS-EPMC84956633377310710.1016/j.immuni.2021.03.006