[PDF][PDF] Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor

H Nishimura, M Nose, H Hiai, N Minato, T Honjo - Immunity, 1999 - cell.com
H Nishimura, M Nose, H Hiai, N Minato, T Honjo
Immunity, 1999cell.com
Abstract 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 …
Abstract
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-2b/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.
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