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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0900227v1 183/6/3932    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Snyder, C. M. Articles by Hill, A. B. PubMed PubMed Citation Articles by Snyder, C. M. Articles by Hill, A. B.

CD4⁺ T Cell Help Has an Epitope-Dependent Impact on CD8⁺ T Cell Memory Inflation during Murine Cytomegalovirus Infection¹

Christopher M. Snyder^2,*, Andrea Loewendorf, Elizabeth L. Bonnett^*, Michael Croft, Chris A. Benedict and Ann B. Hill^*

^* Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, OR 97239; and Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

Murine CMV (MCMV) establishes a systemic, low-level persistent infection resulting in the accumulation of CD8⁺ T cells specific for a subset of viral epitopes, a process called memory inflation. Although replicating virus is rarely detected in chronically infected C57BL/6 mice, these inflationary cells display a phenotype suggestive of repeated Ag stimulation, and they remain functional. CD4⁺ T cells have been implicated in maintaining the function and/or number of CD8⁺ T cells in other chronic infections. Moreover, CD4⁺ T cells are essential for complete control of MCMV. Thus, we wondered whether CD4⁺ T cell deficiency would result in impaired MCMV-specific CD8⁺ T cell responses. Here we show that CD4⁺ T cell deficiency had an epitope-specific impact on CD8⁺ T cell memory inflation. Of the three codominant T cell responses during chronic infection, only accumulation of the late-appearing IE3-specific CD8⁺ T cells was substantially impaired in CD4⁺ T cell-deficient mice. Moreover, the increased viral activity did not drive increased CD8⁺ T cell division or substantial dysfunction in any MCMV-specific population that we studied. These data show that CD4⁺ T cell help is needed for inflation of a response that develops only during chronic infection but is otherwise dispensable for the steady state maintenance and function of MCMV-specific CD8⁺ T cells.

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 Grant R01 A I47206 and an American Heart Association Grant-in-Aid (to A.B.H.) as well as American Heart Association Postdoctoral Training Grant 0725786Z (to C.M.S.) and Deutsche Forschungsgemeinschaft Grant LO 1421/1-1 (to A.L.).

² Address correspondence and reprint requests to Dr. Christopher M. Snyder, Department of Molecular Microbiology and Immunology, Oregon Health and Sciences University, 1381 Southwest Sam Jackson Park Road, Portland, OR 97239. E-mail address: snydechr{at}ohsu.edu

³ Abbreviations used in this paper: MCMV, murine CMV; LCMV, lymphocytic choriomeningitis virus; MHC II, MHC class II; ICS, intracellular cytokine staining; µMT, B6.129S2-Igh-6^tm1Cg/J.