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Thymic Low Affinity/Avidity Interaction Selects Natural Th1 Cells

Identification of intrathymic eomesodermin+ (Eomes+) CD4 T cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. Promyelocytic leukemia zinc finger protein+ T cells and natural Th17 cells are known to be generated by sensing a high and persistent TCR strength, whereas this is not the case for Eomes+ CD4 T cells. These cells go through low-level signal during the entire maturation pathway, which subsequently leads to induction of high susceptibility to cytokine IL-4. This event seems to be a major determinant for the generation of this type of cell. These T cells are functionally equivalent to Th1 cells that are present in the periphery, and this event takes place both in transgenic and in wild-type mice. There is additional evidence that this type of Eomes+ innate CD4 T cell is also present in human cord blood.