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 c ells, we analyzed changes in surface antigen expression by regeneratin g thymocytes after sublethal irradiation. Two-color flow cytofluoromet ric analysis of the regenerating thymocytes revealed that FK506 had fe w 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) MH C class I+ (TCR alpha beta, alpha and beta chains of the T cell antige n 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 adminis tration. Furthermore, three-color analysis also detected a maturationa l defect of CD4(-)8(+) TCR alpha beta(high) cells. Immunohistochemical analysis using MoAbs specific for MHC and TCR alpha beta revealed mar ked atrophy of the thymus medulla, suggesting disturbances in thymocyt e regeneration and maturation. These results suggest that the maturati on of CD4(-)8(-) TCR alpha beta(-) MHC class I- cells to CD4(+)8(+) TC R alpha beta(low) MHC class I+ cells may be FK506 resistant, whereas F K506 may interfere with the maturation of CD4(+)8(+) TCR alpha beta(lo w) 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 cl ass I+ cells. We also demonstrated the possibility of enrichment of CD 4(+)8(-) cells after sublethal irradiation and the existence of small subpopulations of CD4(+)8(-) TCR alpha beta(-) and CD4(-)8(+) TCR alph a beta(-) cells which might mature to CD4(+)8(+) cells in rat thymus.