Helper T-Cell Subsets and Control of the Inflammatory Response

CD4 T cells are critical components of the immune system and key regulators of the inflammatory processes required to limit infection. Decades of research has led to the discovery of multiple CD4 T-cell subsets (T-helper cell 1 [Th1], Th2, Th17, Th9, Th22, Tfh) that promote the function of a broad range of immune cell types, including phagocytes, granulocytes, and other lymphocyte subsets. This is accomplished through direct cell-to-cell interactions and via the production of cytokines. The contributions of CD4 T cells to host protection are highlighted by the clinical conditions of individuals with impaired T-cell responses. Conversely, dysregulation of T-cell responses can result in rampant inflammation and autoimmunity, as seen in a myriad of clinical conditions. Therefore, T cells have the formidable challenge of protecting the host over their lifespan from a myriad of pathogenic organisms while limiting reactions against self antigens. To carry out inflammatory reactions, T cells must transit through several stages or checkpoints. These include antigen recognition and activation, clonal expansion, migration, effector differentiation, and survival or memory. These distinct stages provide control to produce the proper types of inflammation and protection from dysregulated T-cell responses. This chapter will examine the role of CD4 T cells as effectors and regulators of inflammation. The discussion will address the processes required to generate functional T-cell immunity, the pathways regulating established immune responses, and the functional heterogeneity within the T-cell compartment.