A new role for T cells in dampening innate inflammatory responses

Abstract

The inflammatory response is an attempt by a host to protect itself against injurious stimuli and initiate the tissue healing process [1,2]. Although the production of both proand anti-inflammatory mediators which occurs mainly within tissues is a systemic process, the pathophysiological events of inflammation are usually compartmentalized, being different from organ to organ, and between organs and the peripheral blood [3,4]. Inflammation and consequential tissue injury vary according to the nature of the insults (e.g. burns, hemorrhages, trauma, peritonitis), the cellular composition of each tissue (e.g. the types of phagocytes or endothelial cells), the micro-environment (e.g. the localized presence of GM-CSF in the lungs, low levels of arginine in the liver, presence of endotoxins in the gut), and different modes of leukocyte recruitment. High levels of proinflammatory mediators, including interleukin-1 (IL-1), tumor necrosis factor (TNF), gamma interferon (IFN-γ), high mobility group protein-1 (HMGB1), and macrophage migration inhibitory factor (MIF), are produced locally and released into the blood stream to initiate remote organ injury. IL-10 [5] and other anti-inflammatory mediators [6] play essential roles in dampening the inflammatory process. While anti-inflammatory mediators within tissues may not always be sufficient to prevent the initiation of a deleterious inflammatory response in different compartments, the inflammatory response must be actively terminated, because failure to do so results in ‘bystander’ damage to tissues and diseases. such as arthritis or hepatitis. The underlying mechanisms that control excessive acute inflammatory responses are still poorly understood. The role of the adaptive immune system in acute inflammation is also vague and most studies have focused on how the adaptive immune system activates the innate system to control infection. Recent studies, however, have revealed that adaptive immune cells actively dampen initial innate responses. This raises new questions regarding the role of the adaptive immune system in the acute phase of infection and inflammation.