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 Request Permissions Google Scholar Articles by Guan, H. Articles by Nagarkatti, M. PubMed PubMed Citation Articles by Guan, H. Articles by Nagarkatti, M.

Role of CD44 in the Differentiation of Th1 and Th2 Cells: CD44-Deficiency Enhances the Development of Th2 Effectors in Response to Sheep RBC and Chicken Ovalbumin¹

Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209

CD4 T cells can be primarily polarized to differentiate into Th1 or Th2 cells. CD44 is a marker of T cell activation and a property of long-lived memory cells and implicated in cell migration, activation, and differentiation. To date, whether CD44 has a role in regulating Th1-Th2 differentiation has not been determined. In this study, we compared Th1 and Th2 responses in wild-type and CD44-deficient mice in response to sheep RBC and chicken OVA, as well as examined Th1-Th2 differentiation in vivo and in vitro from CD44-sufficient and CD44-deficient naive CD4 T cells. We observed that deficiency of CD44 tended to inhibit Th1 while promoting Th2 differentiation. Furthermore, chimeric studies suggested that CD44 expression by CD4 T cells was essential for such Th2 bias. The regulation by CD44 occurred at the transcription level leading to up-regulated GATA3 and down-regulated T-bet expression in activated CD4 T cells. We also noted that CD44-deficiency could modify the state of dendritic cell subsets to induce a Th2-biased development. Results presented in this study demonstrate for the first time that CD44 participates in the regulation of Th1-Th2 differentiation.

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 study was supported in part by grants from National Institutes of Health AI053703, ES09098, AI058300, DA016545, HL058641, and P01AT003961.

² Address correspondence and reprint requests to Dr. Mitzi Nagarkatti, University of South Carolina, School of Medicine, Department of Pathology, Microbiology and Immunology, 6439 Garners Ferry Road, Columbia, SC 29209. E-mail address: mnagark{at}gw.med.sc.edu

³ Abbreviations used in this paper: DC, dendritic cell; LC, Langerhan cell; DTH, delayed type hypersensitivity; WT, wild type; SRBC, sheep RBC; BM, bone marrow; pDC, plasmacytoid DC; mDC, myeloid DC; LDC, lymphoid DC.