Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor.
PD-1, a 55 kDa transmembrane protein containing an immunoreceptor tyrosine-based inhibitory motif, is induced in lymphocytes and monocytic cells following activation. Aged C57BL/6(B6)-PD-1(-/-) congenic mice spontaneously developed characteristic lupus-like proliferative arthritis and glomerulonephritis with predominant IgG3 deposition, which were markedly accelerated by introduction of a Fas mutation (lpr). Introduction of a PD-1 null mutation into the 2C-TCR (anti-H-2Ld) transgenic mice of the H-2(b/d) background resulted in the chronic and systemic graft-versus-host-like disease. Furthermore, CD8+ 2C-TCR+ PD-1(-/-) T cells exhibited markedly augmented proliferation in vitro in response to H-2d allogenic cells. Collectively, it is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses.
Nishimura
H
H
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Nose
M
M
Hiai
H
H
Minato
N
N
Honjo
T
T
D000818:Animals; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D001172:Arthritis, Rheumatoid / Q000209:etiology*; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics; D007108:Immune Tolerance; D008181:Lupus Nephritis / Q000209:etiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D006183:H-2 Antigens; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins