Tuning virus-specific T cell responses by costimulatory signals

Abstract

T cell responses are highly critical for the control of numerous pathogenic infections. For proper T cell activation, several signals are required, including antigen presentation, interactions mediated via costimulatory receptor/ligand pairs, and cytokine signaling. There are many different costimulatory receptors that upon interaction with specific ligands promote T cell expansion and differentiation. This diverse repertoire of costimulatory molecules, suggests that each costimulatory receptor/ligand interaction has a unique function, nonetheless all interactions impact T cell expansion. It is unclear which signals are essential in a given situation and whether costimulatory molecules have unique or overlapping functions. Besides costimulatory signals, also IL-2 signals and type I IFNs promote T cell expansion. In this thesis, we assess how costimulatory signals, IL-2 and type I IFNs affect virus-specific immunity and determine whether these signals work in a cooperative manner. More understanding of the combined impact of signals that promote T cell expansion and differentiation could be valuable for improving current vaccination settings and immunotherapies.