EVIDENCE THAT CYCLOSPORINE TREATMENT CAUSES THE APPEARANCE IN RAT LYMPH NODE OF T CELLS HAVING THE ANTIGENIC PHENOTYPES OF CORTICAL THYMOCYTESNODE

Abstract

The antigenic phenotypes and relative size distributions of thymocytes and LN cells from young adult M520 strain rats, injected s.c. with cyclosporine (15 mgm/kg) for 10 consecutive days, were determined by FACS analysis and fluorescence microscopy. In addition, the prothymocyte activity in BM from these CsA-treated rats was assayed by i.v. adoptive transfer into sublethally irradiated, but non-CsA-treated, BUF strain recipients. The results showed that short-term CsA treatment causes a selective and almost complete depletion of both the CD4+8- and CD4-8+ subsets of medullary thymocytes, but that this effect is unrelated to any apparent influence of CsA on the proliferative or developmental potential of prothymocytes in the BM of the treated animals. The results also demonstrated that, early in the course of CsA treatment, there is a marked accumulation of LN T cells that display the antigenic phenotypes and size distribution of cortical thymocytes. Approximately 67% of these T cells had a CD4+8+ TdT+ Thy 1+ phenotype; 17% had a CD4-8+ TdT+ Thy 1+ phenotype. These "immature" lymph node T cells expressed the RT7 pan-T cell alloantigen, but lacked the RT6 postthymic T cell subset alloantigen. All were sIg-. In aggregate they were approximately 30% of the total CsA-LN T cells, as compared with fewer than 3% in controls.