Effects of FK506 on surface antigen expression by regenerating thymocytes after sublethal irradiation in the rat.

To determine the effects of FK506 on the intrathymic maturation of T cells, we analyzed changes in surface antigen expression by regenerating thymocytes after sublethal irradiation. Two-color flow cytofluorometric analysis of the regenerating thymocytes revealed that FK506 had few effects on the maturation of rat thymocytes from CD4-8- to CD4+8+, and from TCR alpha beta- MHC class I- to TCR alpha beta low MHC class I+ (TCR alpha beta, alpha and beta chains of the T cell antigen receptor). However, defects in the maturation of CD4+8+ cells to CD4+8- cells and of TCR alpha beta low MHC class I+ cells to TCR alpha beta high MHC class I+ cells were observed after FK506 administration. Furthermore, three-color analysis also detected a maturational defect of CD4-8+ TCR alpha beta high cells. Immunohistochemical analysis using MoAbs specific for MHC and TCR alpha beta revealed marked atrophy of the thymus medulla, suggesting disturbances in thymocyte regeneration and maturation. These results suggest that the maturation of CD4-8- TCR alpha beta- MHC class I- cells to CD4+8+ TCR alpha beta low MHC class I+ cells may be FK506 resistant, whereas FK506 may interfere with the maturation of CD4+8+ TCR alpha beta low MHC class I+ thymocytes not only to CD4+8- TCR alpha beta high MHC class I+ cells but also to CD4-8+ TCR alpha beta high MHC class I+ cells. We also demonstrated the possibility of enrichment of CD4-8- cells after sublethal irradiation and the existence of small subpopulations of CD4+8- TCR alpha beta- and CD4-8+ TCR alpha beta- cells which might mature to CD4+8+ cells in rat thymus.