A two-step model of T cell subset commitment: antigen-independent commitment of T cells before encountering nominal antigen during pathogenic infections.
Pathogenic infections lead to activation of innate immunity followed by induction of a type 1 T cell subset and, therefore, provide a good model to evaluate when T cells commit to type 1 T cells. Here we show a two-step mechanism of T cell subset commitment during pathogenic infection. The first step is mediated by the basal function of macrophage/dendritic cells and is antigen independent. This step modulates the committed precursor frequency of T cell subsets and influences the expression of T-box expressed in T cells (T-bet) and GATA-3 genes. IL-12 and NK cells are not required for this step. The second step requires antigenic stimulation of T cells together with IL-12 or IL-4, and influences on the expression of T-bet and GATA-3. We propose a two-step T cell subset commitment pathway based on these observations. Therefore, pathogenic infections influence functional T cell commitment before T cells encounter nominal antigen.
Kanoh
Makoto
M
Department of Immunology and Host Defenses, Ehime University School of Medicine, Shigenobu, Onsen-gun, Ehime 791-0295, Japan.
Uetani
Teruyoshi
T
Sakan
Hirokazu
H
Maruyama
Saho
S
Liu
Fengzhi
F
Sumita
Kohsuke
K
Asano
Yoshihiro
Y
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens; D002454:Cell Differentiation; D018925:Chemokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D050990:GATA3 Transcription Factor; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000172:deficiency; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008088:Listeriosis / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018448:Models, Immunological; D010047:Ovalbumin / Q000276:immunology; D019707:Receptors, Chemokine / Q000235:genetics; D020825:T-Box Domain Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000098815:T-bet Transcription Factor
D000941:Antigens; D018925:Chemokines; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D019707:Receptors, Chemokine; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin