First Author | Lui JB | Year | 2015 |
Journal | Cell Rep | Volume | 10 |
Issue | 4 | Pages | 574-85 |
PubMed ID | 25640181 | Mgi Jnum | J:277583 |
Mgi Id | MGI:6274064 | Doi | 10.1016/j.celrep.2014.12.053 |
Citation | Lui JB, et al. (2015) Cross-differentiation from the CD8 lineage to CD4 T cells in the gut-associated microenvironment with a nonessential role of microbiota. Cell Rep 10(4):574-85 |
abstractText | 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 TGFbeta 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. |