© The Rockefeller University Press, 0022-1007/1997/5/1725/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 10, May 19, 1997 1725-1733
Regulatory T Cells Specific for the Same Framework 3 Region of the Vβ8.2 Chain Are Involved in the Control of Collagen II–induced Arthritis and Experimental Autoimmune Encephalomyelitis
Vipin Kumar,
Fatema Aziz,
Eli Sercarz, and
Alexander Miller
From the Department of Microbiology and Molecular Genetics, University of California, Los Angeles, California 90095-1489
Recent evidence indicates that chronic autoimmune disease can result from breakdown of regulation and subsequent activation of self-reactive T cells. In many murine autoimmune disease systems and in the Lewis rat, antigen-specific T cells utilizing the T cell receptor (TCR) Vβ8.2 gene segment play a major role. In the myelin basic protein–induced experimental autoimmune encephalomyelitis (EAE) model in H-2u mice, we had shown that T cells recognizing a peptide determinant within the framework 3 region of the Vβ8.2 chain have a critical role in influencing the course of the disease. Here, we report experiments in another disease system, collagen II (CII)–induced arthritis (CIA) in DBA/1LacJ (H-2q) mice, indicating a remarkably parallel control circuit to that found for EAE. A critical role is played by CII-specific Vβ8.2bearing T cells in the CIA system, which we have confirmed. Animals treated with the superantigen SEB before CII administration are significantly protected from CIA. Next, we tested the ability of peptides encompassing the entire Vβ8.2 chain to induce proliferative responses. Only TCR peptide B5 (amino acids 76–101), a regulatory peptide in EAE, induced proliferation. B5 was then used to vaccinate DBA/1LacJ mice and was shown to reduce greatly the severity and incidence of CIA as measured by joint inflammation or histology. Furthermore, similar protection was found when B5 was administered after CII immunization. It was shown that there is physiological induction of a proliferative response to B5 during CIA and that the determinant within B5 is produced from a single chain TCR construct containing the entire Vβ8.2 chain. Finally, the regulation of CIA is discussed in the context of other experimental autoimmune diseases, especially EAE, with emphasis on what appear to be strikingly common mechanisms.
Address correspondence to Dr. Vipin Kumar, Division of Immune Regulation, La Jolla Institute for Allergy and Immunology 10355 Science Center Drive, San Diego, CA 92121.
1Abbreviations used in this paper: bCII, bovine collagen II; CIA, collagen IIinduced arthritis; CII, collagen II; EAE, experimental autoimmune encephalomyelitis; EAN, experimental autoimmune neuritis; EAU, experimental autoimmune uveoretinitis; IRBP, interphotoreceptor retinoid binding protein; MBP, myelin basic protein; NOD, nonobese diabetic; SEA, staphylococcal enterotoxin A; SEB, staphylococcal enterotoxin B; S.I., stimulation index.

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