Thymic nurse cells: a microenvironment for thymocyte development and selection.

Abstract

Thymic nurse cells (TNCs) represent a unique microenvironment in the thymus for MHC restriction and T cell repertoire selection composed of a cortical epithelial cell surrounding 20-200 immature thymocytes. TNCs have been isolated from many classes of animals from fish to humans. Studies performed using TNC lines showed that TNCs bind viable alphabetaTCRlow CD4(+)CD8(+)CD69(-) thymocytes. A subset of the bound cells is internalized, proliferates within the TNC, and matures to the alphabetaTCRhigh CD4(+)CD8(+)CD69(+) stage, indicative of positive selection. A subset of the internalized population is released while cells that remain internalized undergo apoptosis and are degraded by lysosomes within the TNC. A TNC-specific monoclonal antibody added to fetal thymic organ cultures resulted in an 80% reduction in the number of thymocytes recovered, with a block at the double positive stage of development. Together these data suggest a critical role for TNC internalization in thymocyte selection as well as the removal and degradation of negatively selected thymocytes. Recent studies have shown that in addition to thymocytes, peripheral circulating macrophages are also found within the TNC complex and can present antigens to the developing thymocytes. These circulating macrophages could provide a source of self-antigens used to ensure a self-tolerant mature T cell repertoire. A reduction in TNC numbers is associated with a variety of autoimmune diseases including thyroiditis and systemic lupus erythematosis.