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Th1 and Th2 Cells Form Morphologically Distinct Immunological Synapses¹

Timothy J. Thauland^*, Yoshinobu Koguchi^*, Scott A. Wetzel, Michael L. Dustin and David C. Parker^2,*

^* Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR 97239; Division of Biological Sciences and Center for Environmental Health Sciences, University of Montana, Missoula, MT 59812; and Department of Pathology and Program in Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York, NY 10016

The arrangement of molecules at the interface between T cells and APCs is known as the immunological synapse (IS). We conducted experiments with supported planar bilayers and transfected fibroblast APC to examine the IS formed by polarized Th1 and Th2 cells. Th1 cells formed typical "bull’s-eye" IS with a ring of adhesion molecules surrounding MHC/TCR interactions at all Ag concentrations tested, while Th2 cells formed multifocal IS at high concentrations of Ag. At low Ag concentrations, the majority of Th2 cells formed IS with a compact, central accumulation of MHC/TCR, but ICAM-1 was not excluded from the center of the IS. Additionally, CD45 was excluded from the center of the interface between Th1 cells and APC, while CD45 was found at the center of the multifocal IS formed by Th2 cells. Finally, phosphorylated signaling molecules colocalized with MHC/TCR to a greater extent in Th2 IS. Together, our results indicate that the IS formed by Th1 and Th2 cells are distinct in structure, with Th2 cells failing to form bull’s-eye IS.

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 AI050823 (to D.C.P.) and AI43542 (to M.L.D.). T.J.T. was supported by Training Grants EYO7123 from the National Eye Institute and T32 AI07472 from the National Institute for Allergy and Infectious Diseases.

² Address correspondence and reprint requests to Dr. David C. Parker, Department of Molecular Microbiology and Immunology, L220, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239. E-mail address: parkerd{at}ohsu.edu

³ Abbreviations used in this paper: IS, immunological synapse; SMAC, supramolecular activation cluster; cSMAC, central SMAC; MCC, moth cytochrome c; 3D, three dimensional.