期刊
JOURNAL OF IMMUNOLOGY
卷 181, 期 2, 页码 865-868出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.2.865
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资金
- NIAID NIH HHS [AI045025, R01 AI070807, R21 AI059881] Funding Source: Medline
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 unbelped 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.
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