V beta 8.2 transgene expression interferes with development of experimental autoimmune thyroiditis in CBA k/q but not k/k mice.
The thyroiditogenic T cell receptor (TCR) repertoire is not yet well defined in murine experimental autoimmune thyroiditis (EAT). Our recent work has shown that, while V beta 8+ T cells have no major role in EAT induction with mouse thyroglobulin (MTg), V beta 13 may be involved. To examine the effect of skewing the TCR repertoire on EAT development, CBA (H2k) mice were mated with B10.Q mice harboring an ovalbumin-specific V beta 8.2 TCR transgene (trg), and the trg+ mice were backcrossed to CBA. FACS analysis showed that peripheral blood T cells from trg+ mice had about 76 and 90% V beta 8.2+ cells in the CD4+ and CD8+ subsets, respectively, compared with about 15 and 11% in trg- sibs. The transgenic CBA k/k and k/q mice were immunized with MTg and sacrificed 28 days later. In all trg+ mice, anti-MTg titers and T cell proliferative responses to MTg were significantly lowered. However, thyroid infiltration was distinctly different in the two strains of transgenic mice; a significant decrease was seen primarily in k/q, but not k/k, trg+ mice. Thus, skewing the TCR repertoire to overexpress an irrelevant TCR revealed the possession of a less flexible thyroiditogenic TCR repertoire in k/q, but not k/k, mice.
Lomo
L C
LC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Motte
R W
RW
Giraldo
A A
AA
Nabozny
G H
GH
David
C S
CS
Rimm
I J
IJ
Kong
Y M
YM
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA / Q000235:genetics / Q000276:immunology*; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D055503:Protein Multimerization; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013954:Thyroglobulin / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D019076:Transgenes
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin; D013954:Thyroglobulin