The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online
doi:10.1084/jem.20070041
The Journal of Experimental Medicine, Vol. 204, No. 9, 2199-2211
The Rockefeller University Press, 0022-1007 $30.00
© McKinstry et al.
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Article

 Rapid default transition of CD4 T cell effectors to functional memory cells

K. Kai McKinstry1, Susanne Golech2, Won-Ha Lee2, Gail Huston1, Nan-Ping Weng2, and Susan L. Swain1

1 Trudeau Institute, Saranac Lake, NY 12983
2 National Institute on Aging, National Institutes of Health, Baltimore, MD 21224

CORRESPONDENCE K. Kai McKinstry: kmckinstry{at}trudeauinstitute.org

The majority of highly activated CD4 T cell effectors die after antigen clearance, but a small number revert to a resting state, becoming memory cells with unique functional attributes. It is currently unclear when after antigen clearance effectors return to rest and acquire important memory properties. We follow well-defined cohorts of CD4 T cells through the effector-to-memory transition by analyzing phenotype, important functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 d closely resemble canonical memory cells rested for 60 d or longer in the absence of antigen. This is true for both Th1 and Th2 lineages, and occurs whether CD4 T cell effectors rest in vivo or in vitro, suggesting a default pathway. We find that the effector–memory transition at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a cohort of genes uniquely associated with memory cells rested for extended periods.

Abbreviations used: AAD, aminoactinomycin-D; AICD, activation-induced cell death; ICCS, intracellular cytokine staining; MFI, mean fluoresence intensity; PCCF, pigeon cytochrome c fragment; Tg, transgenic.

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