Cutting edge: chromatin remodeling as a molecular basis for the enhanced functionality of memory CD8 T cells.
Memory CD8 T cells, unlike their naive precursors, are capable of rapidly producing high levels of cytokines, killing target cells, and proliferating into numerous secondary effectors immediately upon Ag encounter. This ready-to-respond state contributes to their superior ability to confer protective immunity, yet the underlying molecular basis remains unknown. In this study, we show that memory CD8 T cells have increased histone acetylation compared with naive CD8 T cells; however, those activated without CD4 T cell help ("unhelped") remain hypoacetylated and fail to develop into functional, protective memory. Treatment with a histone deacetylase inhibitor during activation results in increased histone acetylation in unhelped CD8 T cells and restores their ability to differentiate into functional memory cells capable of immediate cytokine production and providing protective immunity. These results demonstrate that CD4 T help-dependent chromatin remodeling provides a molecular basis for the enhanced responsiveness of memory CD8 T cells.
Northrop
John K
JK
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wells
Andrew D
AD
Shen
Hao
H
D000107:Acetylation; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; C012589:trichostatin A; D006655:Histone Deacetylases