Abnormal distribution of T cell subsets in the thymus of cyclosporin A (CsA)-treated mice.

Cyclosporin A (CsA) administration to normal, unprimed BALB/c mice at the dose of 20 mg/kg every other day for 3 weeks markedly reduced the thymus weight as well as the size and cellularity of the thymic medulla with relative preservation of the cortex. Area of the medullary compartment (the ratio of the area of medulla to area of cortex) of the CsA-treated mice decreased to about one half of that of the solvent alone-treated mice. Through the use of monoclonal anti-L3T4 and anti-Lyt-2 antibodies together with two-color flow cytofluorometry, we demonstrated that CsA caused a remarkable reduction of L3T4+ Lyt-2- subset and only a slight increase in L3T4+ Lyt-2+ subset in the thymus. There was no significant difference in the percentage of L3T4- Lyt-2+ subset between the CsA-treated and solvent-treated groups. Additionally, thymocytes from CsA-treated mice showed a marked reduction of in vitro proliferative responses to concanavalin A and phytohemagglutinin. The above mentioned results imply that in normal, unprimed mice CsA may preferentially impair L3T4+ Lyt-2- subset (helper T cells and their precursors) residing in the thymic medulla whereas is much less effective against L3T4+ Lyt-2+ subset present in the cortex and L3T4- Lyt-2+ subset.