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CD43 Regulates Th2 Differentiation and Inflammation¹

Judy L. Cannon^2,3,*, Amélie Collins^2,*, Purvi D. Mody, Diwaker Balachandran^*, Kammi J. Henriksen^*, Cassandra E. Smith, Jiankun Tong^*, Bryan S. Clay, Stephen D. Miller and Anne I. Sperling^*,

^* Department of Medicine, Section of Pulmonary and Critical Care Medicine, and Committee on Immunology, University of Chicago, Chicago, IL 60637; and Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611

CD43 is a highly glycosylated transmembrane protein that regulates T cell activation. CD43^–/– T cells are hyperproliferative and the cytoplasmic tail of CD43 has been found to be sufficient to reconstitute wild-type proliferation levels, suggesting an intracellular mechanism. In this study, we report that upon TCR ligation CD43^–/– T cells demonstrated no increase in tyrosine phosphorylation but a decreased calcium flux. Interestingly, CD43^–/– T cells preferentially differentiated into Th2 cells in vitro, and CD43^–/– T cells show increased GATA-3 translocation into the nucleus. In vivo, CD43^–/– mice exhibited increased inflammation in two separate models of Th2-mediated allergic airway disease. In contrast, in Th1-mediated diabetes, nonobese diabetic CD43^–/– mice did not significantly differ from wild-type mice in disease onset or progression. Th1-induced experimental autoimmune encephalomyelitis to MOG_35–55 was also normal in the CD43^–/– mice. Nonetheless, the CD43^–/– mice produced more IL-5 when restimulated with MOG_35–55 in vitro and demonstrated decreased delayed-type hypersensitivity responses. Together, these data demonstrate that although CD43^–/– T cells preferentially differentiate into Th2 cells, this response is not sufficient to protect against Th1-mediated autoimmune responses.

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 R01 AI44932 (to A.I.S.), and RO1 NS/AI-026543 (to S.D.M.). J.L.C. is supported by a fellowship from the Irvington Institute Fellowship Program of the Cancer Research Institute.

² J.L.C. and A.C. share first authorship.

³ Address correspondence and reprint requests to Dr. Judy L. Cannon, University of Chicago, MC6026 M619, 5841 South Maryland Avenue, Chicago, IL 60637. E-mail address: jlcanno{at}uchicago.edu

⁴ Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; P-Tyr, phosphotyrosine; MOG, myelin oligodendrocyte glycoprotein; eGFP, enhanced GFP; BAL, bronchoalveolar lavage; DTH, delayed-type hypersensitivity; WT, wild type; AAD, allergic airway disease; SEA, schistosome egg Ag.