Superior 3-year kidney graft function in patients with impaired pretransplant Th2 responses.
In a prospective study of 80 patients, we investigated the association of kidney graft rejection with pretransplant CD4 helper/suppressor function, B cell responses, and in vitro cytokine secretion. A pokeweed mitogen-driven allogeneic coculture system was used to assess CD4 helper/suppressor function and T cell-dependent B cell responses. SAC I was used for T cell- and monocyte-independent stimulation of B cell cultures. B cell differentiation was assessed in a reverse hemolytic plaque assay. ELISAs were used to determine in vitro cytokine secretion. None of the 12 patients with pretransplant CD4 helper defects (< 10% helper activity) 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 exhibited better 3-year graft function than patients without CD4 helper defects (serum creatinine of functioning grafts: 1.2 +/- 0.1 mg/dl compared to 1.7 +/- 0.1 mg/dl, P < 0.05). Low pretransplant IL-10 responses (< 100 pg/ml; 14/80 patients) were significantly associated with a low incidence of acute rejection episodes (P < 0.01) and good 3-year graft function (P < 0.05). These data show that impaired pretransplant Th2 responses-CD4 help and IL-10 responses-predict a low risk of kidney graft rejection and good 3-year graft function, whereas Th1 (IL-2, IFN-gamma) and B cell/monocyte responses are not of predictive value.
Department of Transplantation Immunology, University of Heidelberg, Germany.
R
R
Weimer
S
S
Zipperle
V
V
Daniel
S
S
Carl
G
G
Staehler
G
G
Opelz
D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005500:Follow-Up Studies; D006801:Humans; D016867:Immunocompromised Host; D016030:Kidney Transplantation / Q000502:physiology*; D009000:Monocytes / Q000276:immunology*; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011446:Prospective Studies; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors
D016207:Cytokines