n‐Butyrate Anergized Effector CD4 + T Cells Independent of Regulatory T cell Generation or Activity

CD4 + T cell anergy reflects the inability of CD4 + T cells to respond functionally to antigenic stimulation through proliferation or IL‐2 secretion. Histone deacetylase (HDAC) inhibitors have been shown to induce anergy in antigen‐activated CD4 + T cells. However, questions remain if HDAC inhibitors mediate anergy through direct action upon activated CD4 + T cells or through the generation and/or enhancement of regulatory T (T reg ) cells. To assess if HDAC inhibitor n‐butyrate induces anergy independent of the generation or expansion of FoxP3 + T reg cells in vitro , we examine n‐butyrate‐treated murine CD4 + T cells for anergy induction and FoxP3 + T reg activity. Whereas n‐butyrate decreases CD4 + T cell proliferation and IL‐2 secretion, n‐butyrate did not augment FoxP3 protein production or confer a suppressive phenotype upon CD4 + T cells. Collectively, these data suggest that HDAC inhibitors can facilitate CD4 + T cell functional unresponsiveness directly and independently of T reg cell involvement.