title: Cross-differentiation from the CD8 lineage to CD4 T cells in the gut-associated microenvironment with a nonessential role of microbiota.
abstract: CD4 and CD8 T cell lineages differentiate through respective thymic selection processes. Here, we report cross-differentiation from the CD8 lineage to CD4 T cells, but not vice versa, predominantly in the large-intestine-associated microenvironment. It occurred in the absence or distal presence of cognate antigens. This pathway produced MHC-class-I-restricted CD4(+)Foxp3(+) T(reg) (CI-T(reg)) cells. Blocking T cell-intrinsic TGFβ signaling diminished CI-Treg populations in lamina propria, but it did not preclude the CD8-to-CD4 conversion. Microbiota were not required for the cross-differentiation, but the presence of microbiota led to expansion of the converted CD4 T cell population in the large intestine. CI-T(reg) cells did not promote tolerance to microbiota per se, but they regulated systemic homeostasis of T lymphocytes and protected the large intestine from inflammatory damage. Overall, the clonal conversion from the CD8 lineage to CD4 T cell subsets occurred regardless of "self" or "nonself." This lineage plasticity may promote "selfless" tolerance for immune balance.
authors: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Jen Bon
authors: JB
authors: Lui
authors: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Priyadharshini
authors: P
authors: Devarajan
authors: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors: Sarah A
authors: SA
authors: Teplicki
authors: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: zchen@med.miami.edu.
authors: Zhibin
authors: Z
authors: Chen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D005434:Flow Cytometry; D007422:Intestines / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064307:Microbiota / Q000502:physiology*
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