Switch from cyclosporine A to tacrolimus in renal transplant recipients: Impact on Th1, Th2, and monokine responses

We showed previously that pretransplant CD4 helper defects and low in-vitro IL-10 responses predict a low risk of acute kidney graft rejection. To com pare the effect of tacrolimus (Tacr) and cyclosporine A (CsA) on the humora l immune response we assessed T helper function, B cell/monocyte responses and in-vitro cytokine responses (TNF-alpha GM-CSF, IL-1 beta, IL-2, IL-4, I L-6, IL-10) in 20 renal transplant recipients before and 3 months after the y were switched from CsA to Tacr because of hyperlipoproteinemia, hirsutism , or gum hyperplasia. T helper function was assessed using a PWM-driven all ogeneic coculture system of patient T cells together with control B cells. B cell/monocyte responses were determined using a PWM-stimulated allogeneic coculture system, SAC I-stimulated B-cell cultures and LPS-stimulated mono cyte cultures. Immunoglobulin-secreting cell (ISC) responses were assessed in a reverse hemolytic plaque assay, and ELISA were used to determine cytok ine secret ion. Treatment with Tacr resulted in a decreased expression of c ostimulatory ligands and adhesion molecules (T cells: CD40L, p < 0.05; CD28 and CD54, p <less than or equal to> 0.01; B cells: CD25, p = 0.05; CD40, p < 0.001; monocytes: CD40, p < 0.01), which coincided with decreased PHA-st imulated T cell IL-2 responses (398 +/- 153 versus 43 +/- 15 pg/ml, p < 0.0 5), impaired CD4 helper activity (117% +/- 22% versus 73% +/- 19%, p < 0.05 ) and increased CD4 suppressor activity (-120% +/- 25% versus -18% +/- 27%, p = 0.02), We observed enhanced CD4 IL-10 responses (p < 0.01) and LPS-sti mulated monocyte responses (TNF-<alpha>, IL-1 beta, and IL-6, p < 0.005; IL -10, p < 0.05), indicating an increased humoral immune responsiveness under treatment with tacrolimus. Our data show that switching of immunosuppressi ve therapy from CsA to tacrolimus results in suppression of costimulatory l igands, adhesion molecules, Th1 responses and CD4 helper activity. However, enhanced humoral immune responses, Th2 and monokine responses, might have a negative impact on long-term graft function. Human Immunology 61, 884-897 (2000). (C) American Society for Histocompatibility and Immunogenetics, 20 00. Published by Elsevier Science Inc.