title: Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.
abstract: A novel peripheral T cell subset characterized by the expression of a NK marker and invariant TCR encoded by V alpha 14 J alpha 281 gene segments with a 1-base N-region was investigated in relation to autoimmune disease development. First, we observed that invariant V alpha 14+ NK T cells are specifically reduced with aging in C57BL/6 lpr/lpr or MRL lpr/lpr mice, whereas no change was observed in age-matched control C57BL/6 or MRL +/+ mice as determined by FACS analysis and RNase protection assay. This reduction precedes the disease development and could also be detected in other autoimmune disease-prone mice, such as C3H gld/gld and (NZB x NZW)F1 mice. These results suggest that the specific decrease in invariant V alpha 14+ NK T cells correlates strongly with the development of autoimmunity. Second, injection of MRL lpr/lpr mice with anti-V alpha 14 mAb resulted in the early onset and exacerbation of lymphosplenomegaly due to the accumulation of abnormal CD3+ B220+ CD4-CD8- T cells as well as an increase in the titers of anti-dsDNA autoantibodies. These results indicate that V alpha 14+ NK T cells regulate autoimmune responses and play a crucial role in controlling the development of autoimmune diseases.
authors.affiliation: Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, Japan.
authors.forename: M A
authors.initials: MA
authors.lastname: Mieza
authors.forename: T
authors.initials: T
authors.lastname: Itoh
authors.forename: J Q
authors.initials: JQ
authors.lastname: Cui
authors.forename: Y
authors.initials: Y
authors.lastname: Makino
authors.forename: T
authors.initials: T
authors.lastname: Kawano
authors.forename: K
authors.initials: K
authors.lastname: Tsuchida
authors.forename: T
authors.initials: T
authors.lastname: Koike
authors.forename: T
authors.initials: T
authors.lastname: Shirai
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: A
authors.initials: A
authors.lastname: Matsuzawa
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics; D017637:Clonal Deletion; D004198:Disease Susceptibility; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D012260:Ribonucleases; D013045:Species Specificity
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012260:Ribonucleases