Foxp4 is dispensable for T cell development, but required for Interferon gamma recall responses during chronic Toxoplasmosis

Transcription factors regulate T cell fates at every stage of development and differentiation. Members of the Foxp family of forkhead transcription factors are fundamental for normal T lineage development; Foxp3 is required for T regulatory cell generation and function, and Foxp1 is necessary for generation and maintenance of naïve T cells. Foxp4, another member of the Foxp family, is highly homologous to Foxp1 and has been shown to dimerize with Foxp proteins. We report the initial characterization of Foxp4 in T lymphocytes. Foxp4 is expressed in both thymocytes and peripheral CD4+ and CD8+ T cells. We used a CD4Cre mediated approach to evaluate the cell autonomous role for Foxp4 in T lymphocytes. T cell development, peripheral cellularity and cell surface phenotype are normal in the absence of Foxp4. Furthermore Foxp3+ T regulatory cells develop normally in Foxp4 deficient animals, and naïve Foxp4 deficient CD4 T cells can differentiate to inducible T regulatory cells in vitro. In wild-type T cells, expression of Foxp4 increases following activation, but deletion of Foxp4 does not affect T cell proliferative responses or in vitro effector T cell differentiation. In vivo, despite effective control of Toxoplasma gondii infection, IFNγ production during an antigen specific recall response is reduced in the absence of Foxp4. We conclude that Foxp4 is dispensable for T cell development, but necessary for T cell cytokine recall responses to antigen in chronically infected mice.