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

Hiroyuki Nishimura, Masato Nose, Hiroshi Hiai, Nagahiro Minato, Tasuku Honjo

Research output: Contribution to journalArticlepeer-review

1763 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
JournalImmunity
Volume11
Issue number2
DOIs
Publication statusPublished - 1999 Aug

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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