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* Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia PA 19104;
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06437;
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06437; and
The Wistar Institute, Philadelphia, PA 19104
During acute lymphocytic choriomeningitis virus (LCMV) infection, CD8 T cells rapidly expand and differentiate into effectors that are required for viral clearance. The accumulation of activated T cells is greatly reduced in mice lacking the adaptor molecule MyD88. Although MyD88 has generally been considered to indirectly regulate adaptive immune responses by controlling inflammatory cytokine production and Ag presentation in innate immune cells, in this study, we identify an unappreciated cell-intrinsic role for MyD88 in LCMV-specific CD8 T cells. Using reciprocal adoptive transfer models and bone marrow chimeras, we show that Myd88–/– CD8 T cells are defective in their clonal expansion in response to LCMV infection, independent of their environment. Furthermore, we show that while MyD88 is dispensable for initial activation and division of LCMV-specific CD8 T cells during the early stages of viral infection, MyD88-dependent signals are critical for supporting their survival and sustained accumulation.
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 AI-062789 (to L.A.T.), AI-070153 (to D.F.L.), AI-071309 (to E.J.W.), HHSN26620050030C (to E.J.W.), and AI-066232-01 (to S.M.K.); Burroughs-Wellcome Fund 1004313 (to S.M.K.); and the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health (to E.J.W.).
2 These authors are considered co-first authors.
3 These authors are considered co-senior authors.
4 Address correspondence to and reprint requests to: Dr. Laurence A. Turka, University of Pennsylvania, 111 Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA-19104-6144. E-mail address: turka{at}mail.med.upenn.edu
5 Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; WT, wild type; KLRG1, killer cell lectin-like receptor subfamily G.
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