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 Saegusa, K. Articles by Hayashi, Y. Search for Related Content PubMed PubMed Citation Articles by Saegusa, K. Articles by Hayashi, Y.

Autoantigen-Specific CD4⁺CD28^low T Cell Subset Prevents Autoimmune Exocrinopathy in Murine Sjögren’s Syndrome¹

Kaoru Saegusa^*,, Naozumi Ishimaru^*, Kumiko Yanagi^*, Norio Haneji^*, Mizuho Nishino, Miyuki Azuma, Ichiro Saito^* and Yoshio Hayashi^2,*

Departments of ^* Pathology and Pediatric Dentistry, Tokushima University School of Dentistry, Kuramotocho, Tokushima, Japan; and Department of Immunology, National Children’s Medical Reseach Center, Tokyo, Japan

Organ-specific autoimmune exocrinopathy resembling Sjögren’s syndrome (SS) that spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is dependent on Th1-type CD4⁺ T cells. We previously reported that a cleavage product of 120-kDa -fodrin may be an important autoantigen in the pathogenesis of SS in both an animal model and the patients. We demonstrate that in an animal model of SS with overt exocrinopathy, a unique CD4⁺ T cell subset expressing CD28^low is dramatically increased in spleen cells before the disease onset, but that the CD4⁺ T cells of diseased mice were virtually all CD28^high. We found that the spleen cells in these mice before the disease onset showed a significant increase in autoantigen-specific T cell proliferation. Analysis of in vitro cytokine production by spleen cells indicated, before the disease onset, severely impaired production of IL-2 and IFN- in the animal model, whereas high levels of IL-4 were observed. Expression of cytokine genes, including IL-4, IL-10, and TGF-ß, was detected in FACS-sorted CD4⁺CD28^low T cells by RT-PCR analysis. Transfer of CD4⁺CD28^low T cells into the animal model actually prevented the development of autoimmune lesions including autoantibody production. These results suggest that a CD4⁺CD28^low T cell subset that is continuously activated by an organ-specific autoantigen may play a regulatory role in the development of organ-specific autoimmune disease in an animal model of SS.

This article has been cited by other articles:

				T. Yoneda, N. Ishimaru, R. Arakaki, M. Kobayashi, T. Izawa, K. Moriyama, and Y. Hayashi Estrogen Deficiency Accelerates Murine Autoimmune Arthritis Associated with Receptor Activator of Nuclear Factor-{kappa}B Ligand-Mediated Osteoclastogenesis Endocrinology, May 1, 2004; 145(5): 2384 - 2391. [Abstract] [Full Text] [PDF]

				H. Bagavant, C. Thompson, K. Ohno, Y. Setiady, and K. S. K. Tung Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease Int. Immunol., December 1, 2002; 14(12): 1397 - 1406. [Abstract] [Full Text] [PDF]