Spleen Lymphocyte Populations and Expression of Activation Markers in Rats Treated with the Potent New Immunosuppressive Agent FK-506

Rats were immunized systemically with sheep red blood cells (SRBC) and treated with either FK-506 (1 mg/kg/day) or cyclosporin A (CsA) (25 mg/kg/day) for 7 days. Profound (greater than 90%) suppression of the production of splenic IgM-secreting plasma cells and circulating antibody levels was observed in animals receiving either drug. Immunosuppression was accompanied by significant increases in the incidence and absolute numbers of OX8+ (T-cytotoxic/suppressor) lymphocytes in the spleen, and there were corresponding reductions in the W3/25+:OX8 (CD4+:CD8+) ratio. The magnitude of these changes was not affected by drug combination. There were no significant alterations in B cells with either agent, whilst a small but significant increase in the incidence of macrophages was observed in all drug-treated groups. Neither FK-506 nor CsA affected IL-2 receptor (OX39) or MHC class II (OX6) antigen expression. This study demonstrates the remarkable immunosuppressive potency of FK-506 and its underlying capacity, like CsA, to affect regulatory T-lymphocyte subsets in vivo.