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The Journal of Immunology, 2001, 166: 5515-5521.
Copyright © 2001 by The American Association of Immunologists

IL-12 Enhances CD8 T Cell Homeostatic Expansion1

William C. Kieper2, Martin Prlic, Clint S. Schmidt, Matthew F. Mescher and Stephen C. Jameson3

Department of Laboratory Medicine and Pathology, University of Minnesota Center for Immunology, Minneapolis, MN 55455

The size of the T lymphocyte pool is maintained by regulation of T cell production, proliferation, and survival. Under the pressure of a T lymphopenic environment, mature naive T cells begin to proliferate in the absence of Ag, a process called homeostatic expansion. Homeostatic expansion involves TCR recognition of self peptide/MHC ligands, but less is known about the soluble factors that regulate this process. Here we show that IL-12 dramatically enhanced the homeostatic proliferation of CD8 T cells. In contrast, IL-2 had no beneficial effect on homeostatic expansion and, in fact, inhibited T cell expansion induced by IL-12. Using gene-targeted mice, we showed that IL-12 acted directly on the T cells to enhance homeostatic expansion, but that IL-12 cannot override the requirement for TCR interaction with self peptide/MHC ligands in homeostatic expansion. These data indicate that inflammatory cytokines may modulate T cell homeostasis after lymphopenia and have implications for regulation of the T cell repertoire and autoimmunity.




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