HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mekala, D. J. Articles by Geiger, T. L. Search for Related Content PubMed PubMed Citation Articles by Mekala, D. J. Articles by Geiger, T. L.

IL-10-Dependent Suppression of Experimental Allergic Encephalomyelitis by Th2-Differentiated, Anti-TCR Redirected T Lymphocytes¹

Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105

We previously showed that transgenically expressed chimeric Ag-MHC- receptors can Ag-specifically redirect T cells against other T cells. When the receptor’s extracellular Ag-MHC domain engages cognate TCR on an Ag-specific T cell, its cytoplasmic -chain stimulates the chimeric receptor-modified T cell (RMTC). This induces effector functions such as cytolysis and cytokine release. RMTC expressing a myelin basic protein (MBP) 89–101-IA^s- receptor can be used therapeutically, Ag-specifically treating murine experimental allergic encephalomyelitis (EAE) mediated by MBP89-101-specific T cells. In initial studies, isolated CD8⁺ RMTC were therapeutically effective whereas CD4⁺ RMTC were not. We re-examine here the therapeutic potential of CD4⁺ RMTC. We demonstrate that Th2-differentiated, though not Th1-differentiated, CD4⁺ MBP89–101-IA^s- RMTC prevent actively induced or adoptively transferred EAE, and treat EAE even after antigenic diversification of the pathologic T cell response. The Th2 RMTC both Th2-deviate autoreactive T cells and suppress autoantigen-specific T cell proliferation. IL-10 is critical for the suppressive effects. Anti-IL-10R blocks RMTC-mediated modulation of EAE and suppression of autoantigen proliferation, as well as the induction of IL-10 production by autoreactive T cells. In contrast to IL-10, IL-4 is required for IL-4 production by, and hence Th2 deviation of autoreactive T cells, but not the therapeutic activity of the RMTC. These results therefore demonstrate a novel immunotherapeutic approach for the Ag-specific treatment of autoimmune disease with RMTC. They further identify an essential role for IL-10, rather than Th2-deviation itself, in the therapeutic effectiveness of these redirected Th2 T cells.

This article has been cited by other articles:

				R. K. Selvaraj and T. L. Geiger Mitigation of Experimental Allergic Encephalomyelitis by TGF-{beta} Induced Foxp3+ Regulatory T Lymphocytes through the Induction of Anergy and Infectious Tolerance J. Immunol., March 1, 2008; 180(5): 2830 - 2838. [Abstract] [Full Text] [PDF]

				I. Moisini, P. Nguyen, L. Fugger, and T. L. Geiger Redirecting Therapeutic T Cells against Myelin-Specific T Lymphocytes Using a Humanized Myelin Basic Protein-HLA-DR2-{zeta} Chimeric Receptor J. Immunol., March 1, 2008; 180(5): 3601 - 3611. [Abstract] [Full Text] [PDF]

				J. Ochoa-Reparaz, C. Riccardi, A. Rynda, S. Jun, G. Callis, and D. W. Pascual Regulatory T Cell Vaccination without Autoantigen Protects against Experimental Autoimmune Encephalomyelitis J. Immunol., February 1, 2007; 178(3): 1791 - 1799. [Abstract] [Full Text] [PDF]

				D. J. Mekala, R. S. Alli, and T. L. Geiger IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+ T lymphocytes PNAS, August 16, 2005; 102(33): 11817 - 11822. [Abstract] [Full Text] [PDF]