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IL-7 Promotes the Transition of CD4 Effectors to Persistent Memory Cells

JiChu Li, Gail Huston and Susan L. Swain

Trudeau Institute, Inc., Saranac Lake, NY 12983

Address correspondence to S.L. Swain, Trudeau Institute, Inc.,154 Algonquin Ave., Saranac Lake, NY 12983. Phone: (518) 891-3080; Fax: (518) 891-5126; email: sswain{at}trudeauinstitute.org

After transfer to adoptive hosts, in vitro–generated CD4 effectors can become long-lived memory cells, but the factors regulating this transition are unknown. We find that low doses of interleukin (IL) 7 enhance survival of effectors in vitro without driving their division. When in vitro–generated effectors are transferred to normal intact adoptive hosts, they survive and rapidly become small resting cells with a memory phenotype. CD4 effectors generated from wild-type versus IL-7 receptor^-/- mice were transferred to adoptive hosts, including intact mice and those deficient in IL-7. In each case, the response to IL-7 was critical for good recovery of donor cells after 5–7 d. Recovery was also IL-7–dependent in Class II hosts where division was minimal. Blocking antibodies to IL-7 dramatically decreased short-term recovery of transferred effectors in vivo without affecting their division. These data indicate that IL-7 plays a critical role in promoting memory CD4 T cell generation by providing survival signals, which allow effectors to successfully become resting memory cells.

Key Words: cytokines • CD4 T cells • immunity • effector cells • survival

Abbreviations used in this paper: AICD, activation-induced cell death; ATXBM, adult-thymectomized, bone marrow–reconstituted; c, common chain; CFSE, carboxyfluorescein diacetate succinimidyl ester; GFP, green fluorescent protein; HDD, homeostasis-driven division; PCCF, pigeon cytochrome c fragment; PCD, programmed cell death; PI, propidium iodide; Tg, transgenic.

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