Thymic nurse cells forming a dynamic microenvironment in spontaneous thymoma BUF/Mna rats

Abstract

Thymic nurse cells (TNCs) were studied using an animal model, BUF/Mna rats, which spontaneously develop benign thymomas of epithelial origin with age. The unusual increment and high availability of TNCs in this thymus enabled us to analyze TNCs directly either in tissue sections or on smears after enzymatic isolation. No structural or phenotypical abnormality in these TNCs was detected as assessed by electron microscopy and immunohistochemistry. Typical TNCs were widely distributed in the cortical areas but not in the medullary areas. They showed characteristic euchromatic bright nuclei and enclosed intra-TNC cells with an investment of relatively light cytoplasm with abundant small vesicles and rough-endoplasmic reticulum. The intra-TNC cells were mostly double positive (CD4+CD8+) cortical thymocytes, though macrophage populations could also be distinguished by their content of membrane-bounded phagosomes, multivesicular bodies and other inclusion bodies, and by their lack of cytoskeletal keratin filaments. High voltage electron microscopy revealed that intra-TNC cells were separated into several compartments by extremely thin internal veils of the TNC processes. The outer veils of the TNCs were continuous with occasional small gaps through which intra-TNC cells could migrate in and out of the compartments. Immunohistochemical analyses revealed that the TNCs per se were positive for MHC class I and class II, keratin and thymulin, but lacked both lymphocyte and macrophage markers. Among all adhesion molecules tested. ICAM-1 was strongly expressed on almost all TNCs. A minority of TNCs also contained either LFA-1α or LFA-1β positive cells. These results suggest that TNCs may form a rather dynamic microenvironment for T cell development where either nursing or clearance of thymocytes take place, depending on the cellular components of intra-TNC cells. Macrophage populations may also play crucial roles as the third component within TNCs.