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.