Developmental studies on expression of monoclonal antibody-defined cytokeratins by thymic epithelial cells from normal and autoimmune mice.
A major component of the thymic microenvironment is a network of thymic epithelial cells (TEC) which are able to express class II major histocompatibility complex products and to secrete thymic hormones. In the present investigation, we used a panel of anti-cytokeratin (CK) antibodies to establish distinct cytokeratin-defined TEC subsets. Four subpopulations were identified. One, in the cortex, is defined by anti-CK8 and anti-CK18 monoclonal antibodies (MAb). The other three subsets are medullary, two minor ones respectively reactive with anti-CK19 and KL1 monoclonal antibodies (the latter being specific for CK3 and 10), and a major one characterized by negative reaction with the above-mentioned MAb but strongly positive after labeling with a polyclonal (and polyspecific) anti-keratin immunoserum. Ontogenetic studies revealed that the CK8+/18+ TEC subset is the first to be detected in fetal life. Moreover, the numbers of CK3/10+ cells and CK19+ cells decrease in aging normal mice, a phenomenon that seems to occur early in autoimmune mice. We also observed that these two medullary TEC subsets are sensitive to high-dose in vivo treatment with hydrocortisone, which stimulates a dramatic increase in CK3/10+ cells and a certain decrease in CK19+ cells. Our results indicate that a number of mouse TEC subsets can be distinguished by cytokeratin expression. Such a strategy can be applied to analyze TEC sensitivity to drugs and might also be useful to further understanding of differential TEC function regarding intrathymic T-cell differentiation.
Savino
W
W
Department of Immunology, Institute Oswaldo Cruz, Rio de Janeiro, Brazil.
Dardenne
M
M
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001284:Atrophy; D001327:Autoimmune Diseases / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D006854:Hydrocortisone / Q000494:pharmacology; D007633:Keratins / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D007633:Keratins; D006854:Hydrocortisone