Dendritic cells, indoleamine 2,3 dioxygenase and acquired immune privilege

Abstract

Dendritic cells (DCs) are specialized to stimulate T cell immunity. Paradoxically, some DCs suppress T cell responses and activate regulatory T cells. In this review, we focus on a potent counter-regulatory pathway mediated by plasmacytoid DCs (pDCs) expressing the immunosuppressive enzyme indoleamine 2,3 dioxygenase (IDO). IDO-expressing pDCs inhibit effector T cell responses, activate regulatory T cells, and attenuate pro-inflammatory responses in settings of chronic inflammation that manifest in clinical syndromes, such as infectious, allergic, and autoimmune diseases; cancer; and transplantation. Thus, IDO-expressing pDCs create immune privilege and provide novel opportunities to improve immunotherapy in multiple disease syndromes.

Figure 1. Dendritic cells (DCs) acquire antigens and collate inflammatory signals from local tissue microenvironments to elicit distinctive T cell responses

A. During tissue homeostasis immature DCs present antigens in a T cell tolerogenic fashion, and regulatory cytokines such as TGFβ and IL-10 help maintain default counter-regulation in such settings, B. T cell stimulatory inflammation in which DCs mature, and acquire potent T cell stimulatory properties that overcome default T cell regulation and tolerance. Cytokines such as IL-6 promote pro-inflammatory outcomes, including conversion of resting regulatory T cells (Tregs) into helper/effector T_H17-like T cells expressing IL-17. C. T cell regulatory inflammation creates immune privilege in which mature DCs stimulate abortive T cell responses, activate Treg suppressor functions, and block pro-inflammatory cytokine production, in part by promoting the IDO mechanism in DCs.