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CTLA-4 Differentially Regulates the Immunological Synapse in CD4 T Cell Subsets¹

Yale University School of Medicine, Department of Immunobiology, New Haven, CT 06520

Primary murine Th1 and Th2 cells differ in the organization of the immunological synapse, with Th1 cells, but not Th2 cells, clustering signaling molecules at the T cell/B cell synapse site. We sought to determine whether differential costimulatory signals could account for the differences observed. We found that Th2 cells express higher levels of CTLA-4 than Th1 cells, and demonstrated that Th2 cells lacking CTLA-4 are now able to cluster the TCR with the same frequency as Th1 cells. Furthermore, reconstitution of CTLA-4 into CTLA-4-deficient Th2 cells, or into Th1 cells, inhibits the clustering of the TCR. We have also shown that Th2 cells, but not Th1 cells, show variations in the organization of the immunological synapse depending on levels of expression of CD80/CD86 on the APC. These studies demonstrate a unique role for CTLA-4 as a critical regulator of Th2 cells and the immunological synapse.

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 CA38350, A126791, and T32A107019.

² Address correspondence and reprint requests to Dr. Rachael Jackman, Yale School of Medicine, Department of Immunobiology, TAC 540, P.O. Box 208011, New Haven, CT 06520. E-mail address: rachael.jackman{at}yale.edu

³ Abbreviations used in this paper: PKC, protein kinase C; BMDC, bone marrow-derived dendritic cell; DC, dendritic cell; MCC, moth cytochrome c.

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