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Published online before print February 13, 2004

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(Journal of Leukocyte Biology. 2004;75:874-883.)
© 2004 by Society for Leukocyte Biology

Cross-regulation of CD86 by CD80 differentially regulates T helper responses from Mycobacterium tuberculosis secretory antigen-activated dendritic cell subsets

Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India

¹Correspondence: Immunology Group, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi-110-067, India. E-mail: natrajan{at}icgeb.res.in

We report that stimulation of Mycobacterium tuberculosis secretory antigen- and tumor necrosis factor -matured BALB/c mouse bone marrow dendritic cells (BMDCs) with anti-CD80 monoclonal antibody up-regulated CD86 levels on the cell surface. Coculture of these BMDCs with naïve, allogeneic T cells now down-regulated T helper cell type 1 (Th1) responses and up-regulated suppressor responses. Similar results were obtained with splenic CD11c⁺/CD8a^– DCs but not to the same extent with CD11c⁺/CD8a⁺ DCs. Following coculture with T cells, only BMDCs and CD11c⁺/CD8a^– DCs and not CD11c⁺/CD8a⁺ DCs displayed increased levels of surface CD86, and further, coculturing these DCs with a fresh set of T cells attenuated Th1 responses and increased suppressor responses. Not only naïve but even antigen-specific recall responses of the Th1-committed cells were modulated by DCs expressing up-regulated surface CD86. Further analyses showed that stimulation with anti-CD80 increased interleukin (IL)-10 and transforming growth factor-ß-1 levels with a concomitant reduction in IL-12p40 and interferon- levels from BMDCs and CD11c⁺/CD8a^– DCs and to a lesser extent, from CD11c⁺/CD8a⁺ DCs. These results suggest that cross-talk between costimulatory molecules differentially regulates their relative surface densities leading to modulation of Th responses initiated from some DC subsets, and Th1-committed DCs such as CD11c⁺/CD8a⁺ DCs may not allow for such modulation. Cognate antigen-presenting cell (APC):T cell interactions then impart a level of polarization on APCs mediated via cross-regulation of costimulatory molecules, which govern the nature of subsequent Th responses.

Key Words: MTSA • Th1 response • polarization • co-stimulation • cross-talk

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