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CD40-CD40 Ligand Interaction between Dendritic Cells and CD8⁺ T Cells Is Needed to Stimulate Maximal T Cell Responses 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

Stimulation of CD40 on APCs through CD40L expressed on helper CD4⁺ T cells activates and "licenses" the APCs to prime CD8⁺ T cell responses. Although other stimuli, such as TLR agonists, can also activate APCs, it is unclear to what extent they can replace the signals provided by CD40-CD40L interactions. In this study, we used an adoptive transfer system to re-examine the role of CD40 in the priming of naive CD8⁺ T cells. We find an 50% reduction in expansion and cytokine production in TCR-transgenic T cells in the absence of CD40 on all APCs, and on dendritic cells in particular. Moreover, CD40-deficient and CD40L-deficient mice fail to develop endogenous CTL responses after immunization. Surprisingly, the role for CD40 and CD40L are observed even in the absence of CD4⁺ T cells; in this situation, the CD8⁺ T cell itself provides CD40L. Furthermore, we show that although TLR stimulation improves T cell responses, it cannot fully substitute for CD40. Altogether, these results reveal a direct and unique role for CD40L on CD8⁺ T cells interacting with CD40 on APCs that affects the magnitude and quality of CD8⁺ T cell responses.

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 from the National Institutes of Health (to K.L.R.) and core resources supported by the Diabetes Endocrinology Research Center Grant.

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: DC, dendritic cell; LCMV, lymphocytic choriomeningitis virus; Tg, transgenic; WT, wild type; BMDC, bone marrow-derived DC.

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