How costimulation directs regulatory T cell responses

Abstract

The immune system contains regulatory T (Treg) cells, which are specialized in immune suppression to prevent autoimmunity. Understanding the signals that direct Treg cells is essential to improve the treatment of diseases where these cells are involved, such as cancer and autoimmune diseases. This thesis describes responses of human CD4 Treg versus conventional T (Tconv) cells to costimulation, an important process controlling T cell division, survival and effector differentiation, through impact on gene regulation and metabolism. Costimulatory receptors of the CD28 family and the TNF receptor superfamily have distinct modes of signal transduction, leading to different downstream consequences. This thesis specifically focuses on costimulatory effects of the classical costimulatory receptor CD28 versus those of TNFR2 on Treg and Tconv cell gene and protein expression, metabolism and function, as assessed by different omics approaches and follow-up analyses by flow cytometry and functional assays.