Costimulation and Pancreatic Autoimmunity: The PD-1/PD-L Conundrum

Editorial

Rev Diabet Stud, 2006, 3(1):6-10

DOI 10.1900/RDS.2006.3.6

Costimulation and Pancreatic Autoimmunity: The PD-1/PD-L Conundrum

Deepak Yadav, Nora Sarvetnick

The Scripps Research Institute, Department of Immunology, 10446, North Torrey Pines Road, IMM-23, San Diego, California 92037, USA.
Address correspondence to: Deepak Yadav, e-mail: dyadav@scripps.edu.

Keywords: type 1 diabetes, costimulation, autoimmunity, PD-1, PD-L1, PD-L2

Abstract

T cell activation is a complex process that requires a multitude of interactions between antigen-presenting cells (APC) and T cells. The primary signal is provided via the binding of the antigen (Ag) presented by the major histocompatibility complex (MHC) on an APC and the T cell receptor (TCR). This signal determines the specificity of the immune response but it is not sufficient to mount an effective antigen-specific immune response; co-signals are additionally required for that purpose. These co-signals are costimulatory pathways that can be either positive or negative and consequently determine the nature of the immune response. The B7-1/2/CD28 costimulatory axis is one of the most extensively studied positive signaling pathways, and it has been shown that this signal leads to a robust T cell activation, proliferation and survival. In this article we discuss the recently described PD-1/PD-L1/PD-L2 costimulatory axis, whose role in pancreatic autoimmunity is only just becoming more deeply understood. The blockade or deficiency of PD-1 leads to an exacerbation of diabetes, signifying that the role of PD-1 is to provide negative signals to T cells. On the other hand, the PD-1 ligand, PD-L1, has been shown to provide both positive and negative signals. The prediction of the existence of a non-PD-1 receptor on T cells capable of transmitting positive signals further adds to the complex nature of this costimulatory pathway.

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