Pretransplant CD4 helper function and interleukin 10 response predict risk 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/suppressor activity, B-cell responses, and in vitro cytokine secretion. Patients' CD4+ or CD8+ T cells were cocultured with control B cells and pokeweed mitogen for 6 days. SAC I was used for T cell- and monocyte-independent 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 (interleukin [IL]-2, IL-10, gamma-interferon) and B cells/monocytes (IL-6, IL-8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor) were determined in culture supernatants using ELISA. Subsets of CD4+ T cells, CD8+ T cells, and B cells were assessed by flow cytometry. None of 12 patients with pretransplant CD4 helper defects (CD4 helper activity < 10%) had acute rejection episodes, in contrast to 32 of 68 (47%) patients with normal pretransplant CD4 helper function (P = 0.001). Patients with pretransplant CD4 helper defects also had better 1-year graft function than patients without CD4 helper defects (serum creatinine 1.2 +/- 0.1 mg/dl and 1.7 +/- 0.1 mg/dl, respectively, P < 0.05). Pretransplant IL-10 responses were significantly associated with the occurrence of acute rejection episodes (P = 0.001) and impaired 1-year graft function (P < 0.001). All 14 patients with low pretransplant IL-10 responses (< 100 pg/ml) had 1-year serum creatinine values 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-effector (CD11b+), cell counts were significantly associated with the occurrence of infections (P < 0.05). These results show that pretransplant CD4 helper defects and low IL-10 responses predict a low risk of graft rejection, whereas Th1 (IL-2, gamma-interferon) and B-cell/monocyte responses are not of predictive value.
Weimer
R
R
Department of Transplantation Immunology, University of Heidelberg, Germany.
Zipperle
S
S
Daniel
V
V
Carl
S
S
Staehler
G
G
Opelz
G
G
D000208:Acute Disease; D001402:B-Lymphocytes / Q000502:physiology; D001803:Blood Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects; D015235:HLA-B Antigens / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007239:Infections / Q000473:pathology; D016753:Interleukin-10 / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology*; D018655:Lymphocyte Count; D011446:Prospective Studies; D012307:Risk Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000502:physiology
D016207:Cytokines; D015235:HLA-B Antigens; D016753:Interleukin-10