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Summary Antithymocyte globulin (ATG) induction therapy is associated with an increased long‐term risk of infection‐ and cancer‐related death. To analyze long‐term effects of ATG induction on lymphocyte function, we prospectively assessed CD4 helper function, B‐cell/monocyte and cytokine responses in 84 renal transplant recipients (ATG, n = 44) up to 1 year post‐transplant. A PWM‐driven allogeneic coculture system was used to assess helper function of CD4+ T cells and T‐cell‐dependent B‐cell responses. SAC I was used for T‐cell‐independent stimulation of B‐cell cultures. In vitro cytokine secretion and serum soluble CD30 (sCD30) were determined by enzyme‐linked immunosorbent assay (ELISA). ATG induced a persistent decrease of peripheral blood lymphocyte counts compared with non‐ATG treatment because of a predominant decrease of CD4+ T cells (4 months, 1 year; P < 0.0005) which was associated with a decreased CD28 expression (1 year, P = 0.02) and CD4 cell interleukin 2 (IL‐2) response (4 months, P < 0.0005). However, Th2 responses (CD4 help, CD4 cell IL‐4 and IL‐10 responses, sCD30), which proved to be predictive of graft outcome, were not affected, and neither was the secretion of the lymphoma growth factors IL‐6 and IL‐10 by B cells and monocytes. Our data show that ATG induction therapy in immunological high‐risk patients induces a profound long‐term decrease in cell counts and Th1 but not Th2 responses of CD4+ T cells which may explain long‐term effects on infection and post‐transplant lymphoproliferative disease (PTLD) incidence because of inadequate T‐cell control.

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