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Programming for CD8 T Cell Memory Development Requires IL-12 or Type I IFN¹

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

Inflammation can have both positive and negative effects on development of CD8 T cell memory, but the relative contributions and cellular targets of the cytokines involved are unclear. Using CD8 T cells lacking receptors for IL-12, type I IFN, or both, we show that these cytokines act directly on CD8 T cells to support memory formation in response to vaccinia virus and Listeria monocytogenes infections. Development of memory to vaccinia is supported predominantly by IL-12, whereas both IL-12 and type I IFN contribute to memory formation in response to Listeria. In contrast to memory formation, the inability to respond to IL-12 or type I IFN had a relatively small impact on the level of primary expansion, with at most a 3-fold reduction in the case of responses to Listeria. We further show that programming for memory development by IL-12 is complete within 3 days of the initial naive CD8 T cell response to Ag. This programming does not result in formation of a population that expresses killer cell lectin-like receptor G1, and the majority of the resulting memory cells have a CD62L^high phenotype characteristic of central memory cells. Consistent with this, the cells undergo strong expansion upon rechallenge and provide protective immunity. These data demonstrate that IL-12 and type I IFN play an essential early role in determining whether Ag encounter by naive CD8 T cells results in formation of a protective memory population.

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 National Institutes of Health Grants AI34824 (to M.F.M.) and AI38903 (to S.C.J.).

² Address correspondence and reprint requests to Dr. Matthew F. Mescher, Center for Immunology, Box 334 Mayo, 420 Delaware Street S.E., Minneapolis, MN 55455. E-mail address: mesch001{at}umn.edu

³ Abbreviations used in this paper: KLRG1, killer cell lectin-like receptor G1; aAPC, artificial APC; LCMV, lymphocyte choriomeningitis virus; LM, Listeria monocytogenes; LN, lymph node; VV, vaccinia virus; WT, wild type.

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