Editorial

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

Deepak Yadav, Nora Sarvetnick

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.

Fulltext: HTML , PDF (231KB)

This article has been cited by other articles:

	Tolerance Strategies Employing Antigen-Coupled Apoptotic Cells and Carboxylated PLG Nanoparticles for the Treatment of Type 1 Diabetes Prasad S, Xu D, Miller SD Rev Diabet Stud 2012. 9(4):319-327
	PD-1 antibody blocks therapeutic effects of T-regulatory cells in Cockroach antigen-induced allergic asthma McGee HS, Yagita H, Shao Z, Agrawal DK Am J Respir Cell Mol Biol 2009. Nov 9, epub ahead of print
	Changes of B7 family costimulatory molecules and their receptors expression in children with asthma Zu Y, Li C, Li D, Zheng Y, Li J J Appl Clin Pediatr 2009. 24(4):271-273
	Transplantation of NIT-1 cells expressing PD-L1 for treatment of streptozotocin-induced diabetes Wen X, Zhu H, Li L, Li Y, Wang M, Liu J, Yang D, Liao W, Shen G Transplantation 2008. 86(11):1596-1602