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.
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72205, USA. fontebc@gmail.com
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D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation; D018920:Coculture Techniques; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D002087:Butyrates; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D056572:Histone Deacetylase Inhibitors