Mechanisms of T Cell Differentiation and Pathogenicity

Upon activation, CD4+ T cells differentiate in different subsets of effector T helper (Th) cells which produce selective cytokines (IFN-g, IL-17, GM-CSF) and have specialized effector functions. Each subset of Th cells orchestrates a specific immune response dedicated to clear pathogens, but when dysregulated, can also lead to the development of autoimmune and allergic reactions.

CD4+ Th cell differentiation is driven by local cytokine environment. T cells producing IL-17 have been implicated in several autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), and psoriasis. Few years ago, Dr. Bettelli identified the cytokines IL-6, TGF-b and IL-23, which drive the differentiation and pathogenicity of Th17 cells. Recent studies have demonstrated that pathogenic Th cells also secrete GM-CSF. The Bettelli Lab is currently determining whether and how GM-CSF+ Th cells differ from IFN-g+ and IL-17+ Th cells and how they mediate their pathogenic functions in autoimmune diseases.