PRETRANSPLANT CD4 HELPER FUNCTION AND INTERLEUKIN-10 RESPONSE PREDICTRISK OF ACUTE KIDNEY GRAFT-REJECTION

In a prospective study of 80 patients, we investigated the association of acute kidney graft rejection with pretransplant T helper/suppresso r activity, B-cell responses, and in vitro cytokine secretion. Patient s' CD4(+) or CD8(+) T cells were cocultured with control B cells and p okeweed mitogen for 6 days. SAC I was used for T cell- and monocyte-in dependent B-cell stimulation and pokeweed mitogen was used for T cell- dependent B-cell stimulation. B-cell differentiation was assessed in a reverse hemolytic plaque assay. Cytokine responses of T cells (interl eukin [IL]-2, IL-10, gamma-interferon) and B cells/monocytes (IL-6, IL -8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimula ting factor) were determined in culture supernatants using ELISA. Subs ets of CD4(+) T cells, CD8(+) T cells, and B cells were assessed by fl ow cytometry. None of 12 patients with pretransplant CD4 helper defect s (CD4 helper activity < 10%) had acute rejection episodes, in contras t to 32 of 68 (47%) patients with normal pretransplant CD4 helper func tion (P = 0.001). Patients with pretransplant CD4 helper defects also had better 1-year graft function than patients without CD4 helper defe cts (serum creatinine 1.2+/-0.1 mg/dl and 1.7+/-0.1 mg/dl, respectivel y, P < 0.05). Pretransplant IL-10 responses were significantly associa ted with the occurrence of acute rejection episodes (P = 0.001) and im paired 1-year graft function (P < 0.001). All 14 patients with low pre transplant IL-10 responses (< 100 pg/ml) had 1-year serum creatinine v alues of < 1.5 mg/dl. Pretransplant B-cell defects and B cell/monocyte -derived cytokine secretion were not related to the incidence of graft rejection or infectious complications. Pretransplant CD8 suppressor-e ffector (CD11b(+)) cell counts were significantly associated with the occurrence of infections (P < 0.05). These results show that pretransp lant CD4 helper defects and low IL-10 responses predict a low risk of graft rejection, whereas Th1 (IL-2, gamma-interferon) and B-cell/monoc yte responses are not of predictive value.