Selective reduction of V alpha 14+ NK T cells associated with disease development in autoimmune-prone mice.
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.
Mieza
M A
MA
Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, Japan.
Itoh
T
T
Cui
J Q
JQ
Makino
Y
Y
Kawano
T
T
Tsuchida
K
K
Koike
T
T
Shirai
T
T
Yagita
H
H
Matsuzawa
A
A
Koseki
H
H
Taniguchi
M
M
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
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012260:Ribonucleases