TY - JOUR
T1 - Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor
AU - Nishimura, Hiroyuki
AU - Nose, Masato
AU - Hiai, Hiroshi
AU - Minato, Nagahiro
AU - Honjo, Tasuku
N1 - Funding Information:
We thank M. Terada, Y. Tabuchi, and M. Yamamoto for their technical assistance. We thank T. Tanaka for her help in preparation of this manuscript. This work was supported by grants from the Ministry of Education, Science, Sports, and Culture of Japan, from Searle Scientific Research Fellowship, and from Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists.
PY - 1999/8
Y1 - 1999/8
N2 - 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-2L(d)) 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-2(d) 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.
AB - 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-2L(d)) 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-2(d) 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.
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U2 - 10.1016/S1074-7613(00)80089-8
DO - 10.1016/S1074-7613(00)80089-8
M3 - Article
C2 - 10485649
AN - SCOPUS:0033180181
VL - 11
SP - 141
EP - 151
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 2
ER -