| First Author | Chandok MR | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 6 | Pages | 3689-98 |
| PubMed ID | 17785805 | Mgi Jnum | J:152048 |
| Mgi Id | MGI:4355810 | Doi | 10.4049/jimmunol.179.6.3689 |
| Citation | Chandok MR, et al. (2007) A biochemical signature for rapid recall of memory CD4 T cells. J Immunol 179(6):3689-98 |
| abstractText | Mechanisms for the rapid recall response mediated by memory T cells remain unknown. In this study, we present a novel, multiparameter analysis of TCR-coupled signaling and function in resting and activated naive and memory CD4 T cells, revealing a biochemical basis for immunological recall. We identify a striking elevation in expression of the proximal tyrosine kinase Zap70 in resting Ag-specific and polyclonal mouse memory vs naive CD4 T cells that is stably maintained independent of protein synthesis. Elevated Zap70 protein levels control effector function as IFN-gamma production occurs exclusively from the Zap70(high) fraction of activated T cells in vitro and in vivo, and specific down-modulation of Zap70 expression in memory CD4 T cells by small interfering RNA or protein inhibition significantly reduces rapid IFN-gamma production. Downstream of Zap70, we show quantitative differences in distal phosphorylation associated with effector function in naive and memory subsets, with low accumulation of phosphorylation in memory T cells producing IFN-gamma at early time points, contrasting extensive phosphorylation associated with IFN-gamma production following sustained activation of naive T cells. Our results reveal a novel biochemical signature imparted to memory CD4 T cells enabling efficacious responses through increased Zap70 expression and reduced accumulation of downstream signaling events. |
