Limits...
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.

Show MeSH

Related in: MedlinePlus

Physiological induction of a proliferative response to B5 during CIA. DBA/1LacJ mice were immunized with CII for the induction  of CIA. 35 d later, splenic cells were assayed for proliferation in response  to a concentration (7 μM) of different TCR peptides, B1 and B5.  [3H]thymidine incorporation was measured by liquid scintillation counting. There was no significant response to B5 in nonimmunized mice, nor  in mice challenged with HEL, 35 d after immunization. Individual responses of eight individual mice are shown.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196316&req=5

Figure 6: Physiological induction of a proliferative response to B5 during CIA. DBA/1LacJ mice were immunized with CII for the induction of CIA. 35 d later, splenic cells were assayed for proliferation in response to a concentration (7 μM) of different TCR peptides, B1 and B5. [3H]thymidine incorporation was measured by liquid scintillation counting. There was no significant response to B5 in nonimmunized mice, nor in mice challenged with HEL, 35 d after immunization. Individual responses of eight individual mice are shown.

Mentions: Although after peptide immunization (see Fig. 1), a proliferative response was detected only to a single TCR–peptide, B5, in DBA/1LacJ mice, it was important to determine whether B5-specific T cells are activated physiologically during the course of disease, in the absence of any challenge with the peptide itself. Mice were challenged with CII for the induction of CIA. 35 d after primary immunization with CII, at which time mice had already developed arthritic symptoms, peripheral T cells proliferated in vitro in response to B5 (Fig. 6). Proliferative responses to any of the other TCR peptides from the Vβ8.2 chain were not detected. Also, nonimmunized mice as well as mice immunized with HEL showed no response to B5.


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)

Physiological induction of a proliferative response to B5 during CIA. DBA/1LacJ mice were immunized with CII for the induction  of CIA. 35 d later, splenic cells were assayed for proliferation in response  to a concentration (7 μM) of different TCR peptides, B1 and B5.  [3H]thymidine incorporation was measured by liquid scintillation counting. There was no significant response to B5 in nonimmunized mice, nor  in mice challenged with HEL, 35 d after immunization. Individual responses of eight individual mice are shown.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 6: Physiological induction of a proliferative response to B5 during CIA. DBA/1LacJ mice were immunized with CII for the induction of CIA. 35 d later, splenic cells were assayed for proliferation in response to a concentration (7 μM) of different TCR peptides, B1 and B5. [3H]thymidine incorporation was measured by liquid scintillation counting. There was no significant response to B5 in nonimmunized mice, nor in mice challenged with HEL, 35 d after immunization. Individual responses of eight individual mice are shown.
Mentions: Although after peptide immunization (see Fig. 1), a proliferative response was detected only to a single TCR–peptide, B5, in DBA/1LacJ mice, it was important to determine whether B5-specific T cells are activated physiologically during the course of disease, in the absence of any challenge with the peptide itself. Mice were challenged with CII for the induction of CIA. 35 d after primary immunization with CII, at which time mice had already developed arthritic symptoms, peripheral T cells proliferated in vitro in response to B5 (Fig. 6). Proliferative responses to any of the other TCR peptides from the Vβ8.2 chain were not detected. Also, nonimmunized mice as well as mice immunized with HEL showed no response to B5.

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