title: The development of autoimmune inflammatory arthropathy in mice transgenic for the human T cell leukemia virus type-1 env-pX region is not dependent on H-2 haplotypes and modified by the expression levels of Fas antigen.
abstract: Previously, we reported that human T cell leukemia virus type-1 env-pX region-introduced transgenic (pX-Tg) mice develop an inflammatory polyarthropathy. Although autoimmune pathogenesis was suggested, the detailed mechanisms remain to be elucidated. In this report, we examined effects of the MHC and fas genes on the development of the disease. When pX-Tg mice were backcrossed with different inbred strains, the incidence of arthritis differed among strains; 64% and 72% in BALB/cAn (H-2d), 25% and 46% in C3H/HeN (H-2k), and 0% and 2% in C57BL/6J (H-2b) background at 3 and 6 months of age, respectively. Rheumatoid factor levels in the serum correlated with the susceptibility to the disease, whereas IL-1beta and MHC gene expression were similarly elevated in all of these strains, suggesting involvement of immune regulatory genes in this strain difference. However, introduction of the H-2d locus into C57BL/6J pX-Tg mice did not increase the incidence of arthritis, and substitution of the BALB/cAn H-2 locus with the H-2b did not decrease it. The results indicate that the H-2 locus is not the major determinant of the disease. Then, since previous study indicated a defect in Fas-mediated apoptosis of transgenic T cells, the effects of fas gene modification on the disease were examined. The incidence increased when these pX-Tg mice were crossed with lpr/lpr mice, while it decreased when crossed with fas-transgenic mice. These observations suggest that aberration of Fas-mediated apoptosis of peripheral lymphocytes, rather than negative selection in the thymus, is involved in the development of autoimmune arthropathy in pX-Tg mice.
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Japan. iwakura@ims.u-tokyo.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Iwakura
authors.forename: K
authors.initials: K
authors.lastname: Itagaki
authors.forename: C
authors.initials: C
authors.lastname: Ishitsuka
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: A
authors.initials: A
authors.lastname: Matsuzawa
authors.forename: S
authors.initials: S
authors.lastname: Yonehara
authors.forename: S
authors.initials: S
authors.lastname: Karasawa
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: S
authors.initials: S
authors.lastname: Saijo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D017637:Clonal Deletion; D003433:Crosses, Genetic; D004198:Disease Susceptibility; D015752:Genes, env; D016355:Genes, pX; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D012217:Rheumatoid Factor / Q000032:analysis; D013045:Species Specificity; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D019014:fas Receptor; D012217:Rheumatoid Factor