Transcription factor LKLF is sufficient to program T cell quiescence via ac-Myc-dependent pathway

T lymphocytes circulate in a quiescent state until they encounter cognate a ntigen bound to the surface of an antigen-presenting cell. The molecular pa thways that regulate T cell quiescence remain largely unknown. Here we show that forced expression of the lung Kruppel-like transcription factor (LKLF ) in jurkat T cells is sufficient to program a quiescent phenotype characte rized by decreased proliferation, reduced cell size and protein synthesis a nd decreased surface expression of activation markers. Conversely, LKLF-def icient peripheral T cells produced by gene targeting showed increased proli feration, increased cell size and enhanced expression of surface activation markers in vivo. LKLF appeared to function, at least in part, by decreasin g expression of the proto-oncogene encoding c-Myc. Forced expression of LKL F was associated with markedly decreased c-Myc expression. In addition, man y effects of LKLF expression were mimicked by expression of the dominant-ne gative MadMyc protein and rescued by overexpression of c-Myc. Thus, LKLF is both necessary and sufficient to program quiescence in T cells and functio ns, in part, by negatively regulating a c-Myc-dependent pathway.