Kinetics of Thymocyte Subset Development and SelectionRevealed by Cyclosporin A Treatment

摘要

Cyclosporin A (CsA) inhibits the development of mature thymocytes from theirCD4+CD8+precursors, but may allow autoreactive cells to mature. Using 3-color flowcytometry, we have followed the progressive development of thymocytes, includingpotentially autoreactive cells, during CsA treatment. Numbers of CD4+CD8+CD3highthymocytes dropped immediately, suggesting that the generation of these mature thymocyteprecursors, normally dependent upon positive selection, was inhibited by CsA.Numbers of CD4-CD8+thymocytes also declined rapidly, but CD4-CD8+thymocyteswere unaffected lfor 2 days, suggesting that the mature single-positive subsets are notsymmetrically derived from a common GsA-sensitive precursor. An exceptional subset ofCD8 SP thymocytes, expressing CD45RA, did not respond to CsA for about 10 days,indicating that they are distantly derived from a CsA-sensitive precursor. Apoptosis ofTCR-Vβ3+thymocytes caused byMtυ-6, quantified according to the down-regulation ofCD4 and CD8 on immature thymocytes, was partially inhibited by CsA, to maximal effectwithin 24 hours. This did not, however, facilitate their development into mature thymocytes.