TY - JOUR
T1 - Expression of an ovalbumin-specific Vβ8.2 TCR transgene inhibits collagen arthritis in B10.Q mice
AU - Nabozny, Gerald H.
AU - Rimm, Ilonna J.
AU - Griffiths, Marie M.
AU - Luthra, Harvinder S.
AU - David, Chella S.
N1 - Funding Information:
The authors would like to thank Ms Julie Hanson and her staff for the excellent breeding and maintenance of the mice used in this study, and Ms Mary Brandt for preparation of the manuscript. The authors would also like to thank Dr Moses Rodriguez for evaluating the susceptibility of the B10.Q-Vp8.2 Tg mice to TMEV induced demyelinating disease. These studies were supported by NIH grant AR30752, a grant from the Minnesota Chapter of the Arthritis Foundation, and ACS grant IM-641 (I. J. R.). G. H. N. is supported by an Arthritis Foundation Postdoctoral Fellowship. I. J. R. is the recipient of a Clinician-Scientist Award from the American Heart Association and is a Claudia Adams Barr Investigator. M. M. G. is supported by Department of veteran's Affairs medical research funds.
PY - 1995/8
Y1 - 1995/8
N2 - Previous studies have illustrated the importance of T cells bearing αβ TCRs in the induction and development of collagen induced arthritis (CIA) in mice. However, the scope of TCR usage in CIA has yet to be clearly defined. Given the inherent diversity of the TCR repertoire, the relative flexibility of the arthritogenic TCR repertoire specific for type II collagen (CII) is not clear. Therefore, we chose to examine the influence of a highly skewed TCR repertoire on CIA. Arthritis susceptible B10.Q (H-2q) mice were mated with C57L (H-2b) animals expressing an ovalbuminspecific Vβ8.2 TCR transgene (Tg) and Tg+ offspring were further backcrossed to B10.Q. Homozygous H-2a/q, Vβ8.2 Tg+ mice displayed a high level of Vβ8.2+ T cells in peripheral blood. However, expression of some endogenous Vβ TCR, such as Vβ14, was still detected. Upon immunization with bovine CII in adjuvant, Vβ8.2 Tg+ mice were highly resistant to CIA when compared with Tg- littermates. Analysis of sera demonstrated a marked reduction in antibody specific for homologous mouse CII as well as heterologous bovine CII in Tg+ animals. Interestingly, Vβ8.2 Tg+ mice still mounted good antibody responses following immunization with human thyroglobulin, indicating that the skewed TCR repertoire affected anti-CII but not antithyroglobulin responses. Thus, our findings show that constraints placed on the TCR repertoire Inhibit pathogenic responses against CII and suggest that in H-2q mice the arthritogenlc TCR repertoire bears only limited flexibility.
AB - Previous studies have illustrated the importance of T cells bearing αβ TCRs in the induction and development of collagen induced arthritis (CIA) in mice. However, the scope of TCR usage in CIA has yet to be clearly defined. Given the inherent diversity of the TCR repertoire, the relative flexibility of the arthritogenic TCR repertoire specific for type II collagen (CII) is not clear. Therefore, we chose to examine the influence of a highly skewed TCR repertoire on CIA. Arthritis susceptible B10.Q (H-2q) mice were mated with C57L (H-2b) animals expressing an ovalbuminspecific Vβ8.2 TCR transgene (Tg) and Tg+ offspring were further backcrossed to B10.Q. Homozygous H-2a/q, Vβ8.2 Tg+ mice displayed a high level of Vβ8.2+ T cells in peripheral blood. However, expression of some endogenous Vβ TCR, such as Vβ14, was still detected. Upon immunization with bovine CII in adjuvant, Vβ8.2 Tg+ mice were highly resistant to CIA when compared with Tg- littermates. Analysis of sera demonstrated a marked reduction in antibody specific for homologous mouse CII as well as heterologous bovine CII in Tg+ animals. Interestingly, Vβ8.2 Tg+ mice still mounted good antibody responses following immunization with human thyroglobulin, indicating that the skewed TCR repertoire affected anti-CII but not antithyroglobulin responses. Thus, our findings show that constraints placed on the TCR repertoire Inhibit pathogenic responses against CII and suggest that in H-2q mice the arthritogenlc TCR repertoire bears only limited flexibility.
KW - Autoimmune arthritis
KW - T cell repertoire
KW - Type II collagen
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U2 - 10.1093/intimm/7.8.1279
DO - 10.1093/intimm/7.8.1279
M3 - Article
C2 - 7495734
AN - SCOPUS:0028983487
SN - 0953-8178
VL - 7
SP - 1279
EP - 1286
JO - International Immunology
JF - International Immunology
IS - 8
ER -