The Journal of Experimental Medicine
BioLegend: PerCP, PerCP/Cy5.5 Ab Conjugates
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Published online 8 December 2003 doi:10.1084/jem.20030735
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© Rockefeller University Press, 0022-1007/2003/12/1797 $5.00
The Journal of Experimental Medicine, Volume 198, Number 12, 1797-1806

Interleukin 7 Regulates the Survival and Generation of Memory CD4 Cells

Robyn M. Kondrack1, Judith Harbertson1, Joyce T. Tan2, Meghan E. McBreen1, Charles D. Surh2 and Linda M. Bradley1

1 Department of Immunology, The Sidney Kimmel Cancer Center, San Diego, CA 92121
2 Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037

Address correspondence to Linda M. Bradley, Dept. of Immunology, The Sidney Kimmel Cancer Center, 10835 Altman Row, San Diego, CA 92121. Phone: (858) 410-4213; Fax: (858) 450-3251; email: lbradley{at}skcc.org

Cytokines, particularly those of the common {gamma} chain receptor family, provide extrinsic signals that regulate naive CD4 cell survival. Whether these cytokines are required for the maintenance of memory CD4 cells has not been rigorously assessed. In this paper, we examined the contribution of interleukin (IL) 7, a constitutively produced common {gamma} chain receptor cytokine, to the survival of resting T cell receptor transgenic memory CD4 cells that were generated in vivo. IL-7 mediated the survival and up-regulation of Bcl-2 by resting memory CD4 cells in vitro in the absence of proliferation. Memory CD4 cells persisted for extended periods upon adoptive transfer into intact or lymphopenic recipients, but not in IL-7- mice or in recipients that were rendered deficient in IL-7 by antibody blocking. Both central (CD62L+) and effector (CD62L-) memory phenotype CD4 cells required IL-7 for survival and, in vivo, memory cells were comparable to naive CD4 cells in this regard. Although the generation of primary effector cells from naive CD4 cells and their dissemination to nonlymphoid tissues were not affected by IL-7 deficiency, memory cells failed to subsequently develop in either the lymphoid or nonlymphoid compartments. The results demonstrate that IL-7 can have previously unrecognized roles in the maintenance of memory in the CD4 cell population and in the survival of CD4 cells with a capacity to become memory cells.

Key Words: CD4 memory • cell subsets • T cell survival • homeostasis

Abbreviations used in this paper: APC, allophycocyanin; BrdU, bromodeoxyuridine; {gamma}c, common {gamma} chain; ICS, intracellular staining; mIgG, mouse IgG; PCC, pigeon cytochrome c; rIgG, rat IgG.


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