Effect of Cyclosporin A on rat thymus: time course analysis by immunoperoxidase technique and flow cytofluorometry.
The effect of Cyclosporin A (CyA) administration 20 mg/kg body weight i.p. for 3 or 7 days on rat lymphoid tissues, especially on the thymus, and the recovery after stopping CyA treatment were investigated by both immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies against rat lymphocytes: OX6, OX7, OX8, OX18 and W3/25. The marked reduction of thymic medulla with CyA treatment was clearly demonstrated by staining with OX18. This change was maximal 7 to 10 days after the start of CyA administration. The obvious restitution of the thymic medulla occurred about 7 days after stopping CyA and was almost completed within 14 days. Flow-cytofluorometric analysis of the thymus showed that the percentages of positive cells labelled with OX7, OX8, OX18 and W3/25 appeared to be not changed except for OX18 during and after CyA treatment. However, the expression of each antigen per cell changed in the amount; the peak of fluorescence intensity of OX7+ cells showed a temporary shift to the right during CyA treatment. Bright positive cell populations for each OX8 and W3/25 increased relatively during CyA treatment, and reverted to the normal levels soon after stopping the CyA treatment. On the other hand, bright OX18+ cells decreased with CyA treatment, but this change recovered gradually after stopping the CyA treatment. Treatment with CyA gave no significant changes in the flow-cytofluorometric analyses for these antibodies on lymph node cells. Natural killer cell activity and the ability to cause local graft-versus-host reaction were not inhibited with CyA treatment. These results suggest that CyA inhibits the proliferation and differentiation of thymocytes, or that CyA makes thymocytes migrate rapidly from cortex to periphery.