Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation

We report here that the ligand of PD-1 is a member of the B7 gene family

Gordon J. Freeman

2002

Scholarcy highlights

  • The balance of positive and negative signals is of central importance in maximizing the ability of the adaptive immune response to defend the host while maintaining immunologic tolerance and preventing autoimmunity
  • The human and murine PD-1 ligand 1 cDNAs were identified in a B7 homology–based search of expressed sequence tag databases
  • As PD-1 is structurally similar to CTL-associated antigen 4, we hypothesized that the ligand of PD-1 might be a member of the B7 gene family and searched for novel B7 homologues
  • The functional significance of this interaction has been demonstrated in T cell assays, in which engagement of PD-1 by PD-L1 leads to the inhibition of TCR-mediated lymphocyte proliferation and cytokine secretion
  • PD-1 is expressed by B cells and myeloid cells, and the significance of PD-1 in these cell types is evidenced by the autoantibody generation and myeloid hyperplasia of PD-1–deficient mice
  • PD-L1 is expected to act on a wider range of cell types than we have demonstrated in this report
  • Induction of PD-1 ligand 1 expression by cytokines such as IFN-␥ or other inflammatory stimuli could result in attenuation of TCR/CD28–mediated T cell activation

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