Expression of an ovalbumin-specific V{beta}8.2 TCR transgene inhibits collagen arthritis in B10.Q mice |
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Authors: | Nabozny Gerald H; Rimm Ilonna J; Griffiths Marie M; Luthra Harvinder S; David Chella S |
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Institution: | 1 Department of immunology Mayo Graduate School of Medicine Rochester, MN 55905, USA
2 Department of Rheumatology, Mayo Graduate School of Medicine Rochester, MN 55905, USA
3 Division of Pediatric Oncology, Department of Pediatrics, Dana-Farber Cancer Institute and Children's Hospital, Harvard Medical School Boston, MA 02115, USA
4 Research Service, veterans Affairs Medical Center, and Department of Medicine, Division of Rheumatology, University of Utah Salt Lake City, UT 84132, USA |
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Abstract: | Previous studies have illustrated the importance of T cellsbearing ß TCRs in the induction and development ofcollagen induced arthritis (CIA) in mice. However, the scopeof TCR usage in CIA has yet to be clearly defined. Given theinherent diversity of the TCR repertoire, the relative flexibilityof the arthritogenic TCR repertoire specific for type II collagen(CII) is not clear. Therefore, we chose to examine the influenceof a highly skewed TCR repertoire on CIA. Arthritis susceptibleB10.Q (H-2q) mice were mated with C57L (H-2b) animals expressingan ovalbuminspecific Vß8.2 TCR transgene (Tg) andTg+ offspring were further backcrossed to B10.Q. HomozygousH-2a/q, Vß8.2 Tg+ mice displayed a high level of Vß8.2+T cells in peripheral blood. However, expression of some endogenousVß TCR, such as Vß14, was still detected.Upon immunization with bovine CII in adjuvant, Vß8.2Tg+ mice were highly resistant to CIA when compared with Tg–littermates. Analysis of sera demonstrated a marked reductionin antibody specific for homologous mouse CII as well as heterologousbovine CII in Tg+ animals. Interestingly, Vß8.2 Tg+mice still mounted good antibody responses following immunizationwith human thyroglobulin, indicating that the skewed TCR repertoireaffected anti-CII but not antithyroglobulin responses. Thus,our findings show that constraints placed on the TCR repertoireInhibit pathogenic responses against CII and suggest that inH-2q mice the arthritogenlc TCR repertoire bears only limitedflexibility. |
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Keywords: | autoimmune arthritis T cell repertoire type II collagen |
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