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The Lipopolysaccharide Adjuvant Effect on T Cells Relies on Nonoverlapping Contributions from the MyD88 Pathway and CD11c⁺ Cells¹

Department of Immunology, University of Connecticut Health Center, Farmington, CT 06030

Bacterial LPS is a natural adjuvant that induces profound effects on T cell clonal expansion, effector differentiation, and long-term T cell survival. In this study, we delineate the in vivo mechanism of LPS action by pinpointing a role for MyD88 and CD11c⁺ cells. LPS induced long-term survival of superantigen-stimulated CD4 and CD8 T cells in a MyD88-dependent manner. By tracing peptide-stimulated CD4 T cells after adoptive transfer, we showed that for LPS to mediate T cell survival, the recipient mice were required to express MyD88. Even when peptide-specific CD4 T cell clonal expansion was dramatically boosted by enforced OX40 costimulation, OX40 only synergized with LPS to induce survival when the recipient mice expressed MyD88. Nevertheless, these activated, but moribund, T cells in the MyD88^–/– mice acquired effector properties, such as the ability to synthesize IFN-, demonstrating that effector differentiation is not automatically coupled to a survival program. We confirmed this notion in reverse fashion by showing that effector differentiation was not required for the induction of T cell survival. Hence, depletion of CD11c⁺ cells did not affect LPS-driven specific T cell survival, but CD11c⁺ cells were paramount for optimal effector T cell differentiation as measured by IFN- potential. Thus, LPS adjuvanticity is based on MyD88 promoting T cell survival, while CD11c⁺ cells support effector T cell differentiation.

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 R01-AI42858, R01-AI52108, P01-AI56172 Project 3 (to A.T.V.) and R01-AI41576, P01-AI56172 Project 1 (to L.L.).

² Address correspondence and reprint requests to Dr. Anthony T. Vella, University of Connecticut Health Center, Room L-3057, Farmington, CT 06030. E-mail address: vella{at}uchc.edu

³ Abbreviations used in this paper: DC, dendritic cell; Tg, transgenic; BSS, balanced salt solution; SEA, staphylococcal enterotoxin A; PLN, peripheral lymph node; WT, wild type; DT, diphtheria toxin; DTR, DT receptor; FL-pep, flagellin peptide.