T cell differentiation within thymic nurse cells.

Thymic nurse cells (TNC), defined as in vitro isolation products of thymic tissue, are epithelial cells harboring in their cytoplasm up to 200 intact, actively dividing thymocytes which are completely surrounded by vacuolar membranes. The TNC plasma membrane expresses major histocompatibility complex class I (H-2 K/D) and class II (I-A) antigens. The expression of MHC class I and class II antigens on the TNC vacuolar membranes was investigated with an improved in situ labeling technique. The major histocompatibility complex phenotype of the vacuolar membranes is H-2 K/D+, I-A2+ and thus identical to the TNC plasma membrane phenotype. By using the labeling technique, the TNC thymocyte population was examined for expression of the T cell differentiation antigens Thy-1, peanut agglutinin, Lyt-1, and Lyt-2, and the antigen expression was related to resistance of this population to cortisone. The majority of TNC thymocytes in individual TNC were cortisone-sensitive and expressed the immature phenotype of cortical thymocytes (Thy-1hi, PNAhi, Lyt-1lo, Lyt-2). A minority of the TNC thymocytes were cortisone-resistant and expressed a mature phenotype (Thy-1lo, peanut agglutininlo, Lyt-1hi). The existence of this minor mature population was confirmed in vivo: cortisone-resistant thymocytes were associated with cortical epithelial cells scattered throughout the thymic cortex of mice treated with dexamethasone. The major histocompatibility complex positive microenvironment of TNC and the heterogeneity in phenotype and resistance to cortisone of the TNC thymocytes, which is related to the state of maturation, indicate that TNC play an important role in the selection and differentiation of T cells.