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Regulatory T cells specific for the same framework 3 region of the Vbeta8.2 chain are involved in the control of collagen II-induced arthritis and experimental autoimmune encephalomyelitis.

Kumar V, Aziz F, Sercarz E, Miller A - J. Exp. Med. (1997)

Bottom Line: Animals treated with the superantigen SEB before CII administration are significantly protected from CIA.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 Vbeta8.2 chain.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, University of California, Los Angeles, California 90095-1489, USA.

ABSTRACT
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) Vbeta8.2 gene segment play a major role. In the myelin basic protein-induced experimental autoimmune encephalomyelitis (EAE) model in H-2(u) mice, we had shown that T cells recognizing a peptide determinant within the framework 3 region of the Vbeta8.2 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-2(q)) mice, indicating a remarkably parallel control circuit to that found for EAE. A critical role is played by CII-specific Vbeta8.2-bearing 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 Vbeta8.2 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 Vbeta8.2 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.

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DBA/1LacJ mice challenged with TCR peptide B5, after  CII immunization, are significantly protected from CIA. After immunization with bovine CII, mice in each group (n = 9) were challenged with  B5/IFA (□) or B4/IFA (♦) on days +10, +20, +30 (A), or days +30,  +40, +50 (B) relative to primary immunization with CII/CFA. These  immunizations were done as described in the legend for Fig. 2.
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Figure 3: DBA/1LacJ mice challenged with TCR peptide B5, after CII immunization, are significantly protected from CIA. After immunization with bovine CII, mice in each group (n = 9) were challenged with B5/IFA (□) or B4/IFA (♦) on days +10, +20, +30 (A), or days +30, +40, +50 (B) relative to primary immunization with CII/CFA. These immunizations were done as described in the legend for Fig. 2.

Mentions: We have tested several variations of the B5 vaccination protocol described in the legend for Fig. 2. Mice injected only once with 14 nmol of B5 in IFA are not protected from CIA. Furthermore, mice given only a single injection of B5 even at a much higher concentration (50 nmol) are not protected, but rather appear to have increased severity of the disease (data not shown). Finally, we have asked whether treatment with B5 after CII injection can protect mice from CIA. In two independent experiments, DBA/ 1LacJ mice challenged with B5 post-CII priming (days +10, +20, +30, Fig. 3 A; or days +30, +40, +50, Fig. 3 B) show significant amelioration of disease. These data clearly establish that B5-specific T cells are able to down modulate CIA, even after CII-induced disease has been initiated.


Regulatory T cells specific for the same framework 3 region of the Vbeta8.2 chain are involved in the control of collagen II-induced arthritis and experimental autoimmune encephalomyelitis.

Kumar V, Aziz F, Sercarz E, Miller A - J. Exp. Med. (1997)

DBA/1LacJ mice challenged with TCR peptide B5, after  CII immunization, are significantly protected from CIA. After immunization with bovine CII, mice in each group (n = 9) were challenged with  B5/IFA (□) or B4/IFA (♦) on days +10, +20, +30 (A), or days +30,  +40, +50 (B) relative to primary immunization with CII/CFA. These  immunizations were done as described in the legend for Fig. 2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196316&req=5

Figure 3: DBA/1LacJ mice challenged with TCR peptide B5, after CII immunization, are significantly protected from CIA. After immunization with bovine CII, mice in each group (n = 9) were challenged with B5/IFA (□) or B4/IFA (♦) on days +10, +20, +30 (A), or days +30, +40, +50 (B) relative to primary immunization with CII/CFA. These immunizations were done as described in the legend for Fig. 2.
Mentions: We have tested several variations of the B5 vaccination protocol described in the legend for Fig. 2. Mice injected only once with 14 nmol of B5 in IFA are not protected from CIA. Furthermore, mice given only a single injection of B5 even at a much higher concentration (50 nmol) are not protected, but rather appear to have increased severity of the disease (data not shown). Finally, we have asked whether treatment with B5 after CII injection can protect mice from CIA. In two independent experiments, DBA/ 1LacJ mice challenged with B5 post-CII priming (days +10, +20, +30, Fig. 3 A; or days +30, +40, +50, Fig. 3 B) show significant amelioration of disease. These data clearly establish that B5-specific T cells are able to down modulate CIA, even after CII-induced disease has been initiated.

Bottom Line: Animals treated with the superantigen SEB before CII administration are significantly protected from CIA.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 Vbeta8.2 chain.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, University of California, Los Angeles, California 90095-1489, USA.

ABSTRACT
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) Vbeta8.2 gene segment play a major role. In the myelin basic protein-induced experimental autoimmune encephalomyelitis (EAE) model in H-2(u) mice, we had shown that T cells recognizing a peptide determinant within the framework 3 region of the Vbeta8.2 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-2(q)) mice, indicating a remarkably parallel control circuit to that found for EAE. A critical role is played by CII-specific Vbeta8.2-bearing 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 Vbeta8.2 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 Vbeta8.2 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.

Show MeSH
Related in: MedlinePlus