Human Memory, but Not Naive, CD4+ T Cells Expressing Transcription Factor T-bet Might Drive Rapid Cytokine Production.

We found that after stimulation for a few hours, memory but not naive CD4+ T cells produced a large amount of IFN- γ; however, the mechanism of rapid response of memory CD4+ T cells remains undefined. We compared the expression of transcription factors in resting or activated naive and memory CD4+ T cells and found that T-bet, but not pSTAT-1 or pSTAT-4, was highly expressed in resting memory CD4+ T cells and that phenotypic characteristics of T-bet+CD4+ T cells were CD45RAlowCD62Llow CCR7low. After short-term stimulation, purified memory CD4+ T cells rapidly produced effector cytokines that were closely associated with the pre-existence of T-bet. By contrast, resting naive CD4+ T cells did not express T-bet, and they produced cytokines only after sustained stimulation. Our further studies indicated that T-bet was expressed in the nuclei of resting memory CD4+ T cells, which might have important implications for rapid IFN-γ production. Our results indicate that the pre-existence and nuclear mobilization of T-bet in resting memory CD4+ T cells might be a possible transcriptional mechanism for rapid production of cytokines by human memory CD4+ T cells. [ABSTRACT FROM AUTHOR]