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Overexpression of Interleukin (IL)-7 Leads to IL-15–independent Generation of Memory Phenotype CD8⁺ T Cells

William C. Kieper¹, Joyce T. Tan¹, Brea Bondi-Boyd¹, Laurent Gapin², Jonathan Sprent¹, Rhodri Ceredig³ and Charles D. Surh¹

¹ Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
² Division of Developmental Immunology, The La Jolla Institute for Allergy and Immunology, San Diego, CA 92121
³ U548 INSERM, CEA-Grenoble, F-38054 Grenoble, France

Address correspondence to Charles D. Surh, Dept. of Immunology, IMM-26, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Phone: 858-784-2006; Fax: 858-784-8227; E-mail: csurh{at}scripps.edu

Transgenic (TG) mice expressing a high copy number of interleukin (IL)-7 cDNA under the control of the major histocomaptability complex (MHC) class II promoter display a 10–20-fold increase in total T cell numbers. Here, we show that the increase in T cell numbers in IL-7 TG mice is most apparent at the level of memory phenotype CD44^hi CD122^hi CD8⁺ cells. Based on studies with T cell receptor (TCR) TG mice crossed to IL-7 TG mice, increased levels of IL-7 may provide costimulation for TCR recognition of self-MHC ligands and thus cause naive CD8⁺ cells to proliferate and differentiate into memory phenotype cells. In addition, a marked increase in CD44^hi CD122^hi CD8⁺ cells was found in IL-7 TG IL-15^- mice. Since these cell are rare in normal IL-15^- mice, the dependency of memory phenotype CD8⁺ cells on IL-15 can be overcome by overexpression of IL-7.

Key Words: T lymphocytes • homeostasis • cytokines • mice • transgenic

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