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CD40 on APCs Is Needed for Optimal Programming, Maintenance, and Recall of CD8⁺ T Cell Memory Even in the Absence of CD4⁺ T Cell Help¹

Maria Genevive H. Hernandez^*,, Lianjun Shen^* and Kenneth L. Rock^2,*

^* Department of Pathology and Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655

CD40 stimulation is one of the many signals that can activate APCs and we have recently shown it to have a unique function in generating maximum primary CD8⁺ T cell responses. However, whether CD40 signaling plays a role in memory CD8⁺ T cell responses is still not completely understood. In this study, we show that in the absence of CD40 on all APCs or specifically on dendritic cells, memory CD8⁺ T cells are generated but at significantly reduced levels. This reduction is due to a contribution of CD40 at several different steps in the generation of CD8⁺ memory. In the initial T cell response, CD40 contributes to maximizing not only the number of effector cells that are generated but also the programming of ones that will differentiate into memory. Subsequently, CD40 is needed to maintain maximal numbers of the committed memory cells in a manner that is independent of the immunizing Ag. Finally, when memory CD8⁺ T cells are reactivated there is a variable requirement for CD40 depending on whether CD40 or CD4⁺ Th cells were present during the primary response. Therefore, CD40 signaling on APCs plays an important role in all phases of a memory CD8⁺ T cell response.

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 grants to K.L.R. from the National Institutes of Health. Core resources supported by Diabetes Endocrinology Research Center Grant DK32520 were also used.

² Address correspondence and reprint requests to Dr. Kenneth L. Rock, Department of Pathology, University of Massachusetts Medical School, Room S2-109, 55 Lake Avenue North, Worcester, MA 01655. E-mail address: kenneth.rock{at}umassmed.edu

³ Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; DC, dendritic cell; Tg, transgenic; WT, wild type; MFI, mean fluorescence intensity.