Thymic Nurse Cells: a Site for Positive Selection and Differentiation of T Cells

Abstract

The capacity to discriminate between “self” and “non-self” is acquired in the thymus where T cell progenitors develop to mature, antigen specific, self-tolerant T cells (Fink and Bevan 1978, Zinkernagel 1978). This process is based on the direct contact of developing T cells with stroma cells and extracellular matrix constituents and the action of humoral factors secreted by nonlymphoid and lymphoid thymic components (von Boehmer et al. 1989, Marrack and Kappler, 1988). The most widely — albeit not exclusively — accepted hypothesis postulates that thymocytes expressing T cell receptors (TCR) with affinity to MHC class I and II molecules displayed on cortical epithelial cells are positively selected (MHC restriction) (Benoist and Mathis 1989, Bill and Palmer 1989). In the medulla the interaction with (auto)antigen presenting bone marrow derived dendritic cells and/or macrophages entails clonal deactivation and/or deletion of T cells expressing potentially harmful TCR (negative selection) (Miller et al. 1989, von Boehmer et al. 1989). The exact sites of positive and negative selection are not yet known. However, thymic nurse cells (TNC) seem to provide an optimal microenvironment for the former (for review see Kyewski 1986). If they are also involved in negative selection is still an open question.