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Augmented IL-7 Signaling during Viral Infection Drives Greater Expansion of Effector T Cells but Does Not Enhance Memory¹

Joseph C. Sun^2,*,, Sophie M. Lehar^3,*, and Michael J. Bevan^4,*

^* Department of Immunology and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; and Division of Immunology, University of California, Berkeley, CA 94143

IL-7 signals are crucial for the survival of naive and memory T cells, and the IL-7R is expressed on the surface of these cells. Following viral infection, the IL-7R is expressed on only a subset of effector CD8 T cells, and has been demonstrated to be important for the survival of these memory precursors. IL-7 message levels remain relatively constant during the T cell response to lymphocytic choriomeningitis virus, but a short-lived burst of GM-CSF is observed soon after infection. Retroviral expression of a chimeric GM-CSF/IL-7R, in which binding of GM-CSF by T cells leads to IL-7 signaling, allows for the delivery of an IL-7 signal in all effector T cells expressing the receptor. In mice infected with lymphocytic choriomeningitis virus, CD8 and CD4 T cells transduced with this chimeric receptor underwent an enhanced proliferative response compared with untransduced populations in the same host. Similarly, TCR transgenic CD8 cells expressing the chimeric receptor produced higher effector numbers during the peak of the T cell response to infection. Surprisingly, the enhanced proliferation did not lead to higher memory numbers, as the subsequent contraction phase was more pronounced in the transduced cell populations. These findings demonstrate that artificial IL-7 signaling during an infection leads to significantly increased Ag-specific effector T cell numbers, but does not result in increased numbers of memory progeny. The extent of contraction may be dictated by intrinsic factors related to the number of prior cell divisions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the National Institutes of Health, AI19335, and the Howard Hughes Medical Institute.

² Current address: Dr. Joseph C. Sun, Department of Microbiology and Immunology, University of California, 513 Parnassus Avenue, HSE 1001B, San Francisco, CA 94143.

³ Current address: Division of Immunology, University of California, 489 Life Science Addition, Berkeley, CA 94720.

⁴ Address correspondence and reprint requests to Dr. Michael J. Bevan, Howard Hughes Medical Institute, Department of Immunology, University of Washington, Box 357370, Seattle, WA 98195. E-mail address: mbevan{at}u.washington.edu

⁵ Abbreviations used in this paper: _c, common -chain; GMR, GM-CSF receptor; GP, glycoprotein; NP, nucleoprotein; HPRT, hypoxanthine phosphoribosyltransferase; huCD2, human CD2; LCMV, lymphocytic choriomeningitis virus; p-STAT, phosphorylated STAT.

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