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The Journal of Immunology, 2004, 172: 2778-2784.
Copyright © 2004 by The American Association of Immunologists

CD86 and CD80 Differentially Modulate the Suppressive Function of Human Regulatory T Cells1

Yong Zheng, Claire N. Manzotti, Michael Liu, Fiona Burke, Karen I. Mead and David M. Sansom2

Medical Research Council Center for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom

Regulatory T cells (Treg) are important in maintaining tolerance to self tissues. As both CD28 and CTLA-4 molecules are implicated in the function of Treg, we investigated the ability of their two natural ligands, CD80 and CD86, to influence the Treg-suppressive capacity. During T cell responses to alloantigens expressed on dendritic cells, we observed that Abs against CD86 potently enhanced suppression by CD4+CD25+ Treg. In contrast, blocking CD80 enhanced proliferative responses by impairing Treg suppression. Intriguingly, the relative expression levels of CD80 and CD86 on dendritic cells are modulated during progression from an immature to a mature state, and this correlates with the ability of Treg to suppress responses. Our data show that CD80 and CD86 have opposing functions through CD28 and CTLA-4 on Treg, an observation that has significant implications for manipulation of immune responses and tolerance in vivo.




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