Harnessing immune regulation for treatment of human diseases : CD4+CD25+ regulatory T cells & antibody glycosylation

Abstract

This thesis consists of two parts, focusing on CD4+CD25+ regulatory T cells (Tregs) (Part I) and IgG glycosylations (Part II), respectively. Part I (Chapter 2-5) is mainly dedicated to a better identification/characterization and generation of functional human Tregs in vitro. In Chapter 2, we investigated the dynamics of endogenous FOXP3 expression and its relation to the suppressive function in activated human CD4+ T cells. In Chapter 3, we discovered an inverse correlation between membrane-bound TNF-alpha expression and cell suppressive abilities within human CD4+CD25++ T-cell compartment. In Chapter 4 & 5, we developed efficient approaches to consistently convert effector T cells into Tregs both in mice and humans. The underlying mechanisms responsible for the inconsistency in Treg conversion were unraveled as well. Part II (Chapter 6-7) aims to analyze the glycosylation pattern of antigen-specific antibodies and to obtain more insights on how glycosylation is regulated during an active immune response. Chapter 6 describes a method for the microscale purification and Fc-glycosylation analysis of auto-antibodies in patients with rheumatoid arthritis. In Chapter 7, we identified, by using an in vitro culture system, some factors that can influence the gylcan pattern of secreted IgG1 during the activation and differentiation of B cells.