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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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Vaccination with TCR–peptide B5 reduces severity and incidence of CIA. Groups of DBA/1LacJ mice (eight in each group) were  immunized subcutaneously with 100 μg of CII in one hind footpad. Disease was monitored in the three remaining limbs in a double-blind manner by two individuals. Each limb was graded with a score of 1 through 4,  the maximum score being 12 for each mouse. The mean arthritis index  was determined by summation of the total score of each joint in each  group of mice and dividing by the total number of animals in each group.  For vaccination experiments, mice were injected with 7 nmol B5/IFA at  days −10 and +10 with respect to the primary CII injection (○). Control  mice were immunized with PBS/IFA (•).
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Figure 2: Vaccination with TCR–peptide B5 reduces severity and incidence of CIA. Groups of DBA/1LacJ mice (eight in each group) were immunized subcutaneously with 100 μg of CII in one hind footpad. Disease was monitored in the three remaining limbs in a double-blind manner by two individuals. Each limb was graded with a score of 1 through 4, the maximum score being 12 for each mouse. The mean arthritis index was determined by summation of the total score of each joint in each group of mice and dividing by the total number of animals in each group. For vaccination experiments, mice were injected with 7 nmol B5/IFA at days −10 and +10 with respect to the primary CII injection (○). Control mice were immunized with PBS/IFA (•).

Mentions: In an attempt to influence the course of CIA, DBA/1LacJ mice were vaccinated with 7 nmol of B5/IFA twice, before challenge with bCII. Mice in the control group were challenged with PBS/IFA or B4/IFA. The effect of vaccination on the severity as well as on the incidence of arthritis was examined in double-blind experiments. We have performed three different experiments with 5–8 mice in each group. A representative experiment with B5 vaccination is shown in Fig. 2. In Table 2, data pooled from three independent experiments are shown: 34 of 36 mice in the control groups (PBS/IFA and B4/IFA) developed severe arthritis by 8–9 wk after CII immunization, whereas only 6 of 18 mice in the B5-vaccinated group displayed CIA. Importantly, B5-vaccinated mice contracted less severe arthritis than mice in the control group (Table 2). A majority of animals in the control group developed severe arthritic symptoms in both front and hind limbs. In contrast, arthritic symptoms were rarely detected in the front limbs of mice vaccinated with B5. These data demonstrate the efficacy of B5-specific T cells in modulating CIA in DBA/1LacJ mice.


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)

Vaccination with TCR–peptide B5 reduces severity and incidence of CIA. Groups of DBA/1LacJ mice (eight in each group) were  immunized subcutaneously with 100 μg of CII in one hind footpad. Disease was monitored in the three remaining limbs in a double-blind manner by two individuals. Each limb was graded with a score of 1 through 4,  the maximum score being 12 for each mouse. The mean arthritis index  was determined by summation of the total score of each joint in each  group of mice and dividing by the total number of animals in each group.  For vaccination experiments, mice were injected with 7 nmol B5/IFA at  days −10 and +10 with respect to the primary CII injection (○). Control  mice were immunized with PBS/IFA (•).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Vaccination with TCR–peptide B5 reduces severity and incidence of CIA. Groups of DBA/1LacJ mice (eight in each group) were immunized subcutaneously with 100 μg of CII in one hind footpad. Disease was monitored in the three remaining limbs in a double-blind manner by two individuals. Each limb was graded with a score of 1 through 4, the maximum score being 12 for each mouse. The mean arthritis index was determined by summation of the total score of each joint in each group of mice and dividing by the total number of animals in each group. For vaccination experiments, mice were injected with 7 nmol B5/IFA at days −10 and +10 with respect to the primary CII injection (○). Control mice were immunized with PBS/IFA (•).
Mentions: In an attempt to influence the course of CIA, DBA/1LacJ mice were vaccinated with 7 nmol of B5/IFA twice, before challenge with bCII. Mice in the control group were challenged with PBS/IFA or B4/IFA. The effect of vaccination on the severity as well as on the incidence of arthritis was examined in double-blind experiments. We have performed three different experiments with 5–8 mice in each group. A representative experiment with B5 vaccination is shown in Fig. 2. In Table 2, data pooled from three independent experiments are shown: 34 of 36 mice in the control groups (PBS/IFA and B4/IFA) developed severe arthritis by 8–9 wk after CII immunization, whereas only 6 of 18 mice in the B5-vaccinated group displayed CIA. Importantly, B5-vaccinated mice contracted less severe arthritis than mice in the control group (Table 2). A majority of animals in the control group developed severe arthritic symptoms in both front and hind limbs. In contrast, arthritic symptoms were rarely detected in the front limbs of mice vaccinated with B5. These data demonstrate the efficacy of B5-specific T cells in modulating CIA in DBA/1LacJ mice.

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