title: ATG induction in renal transplant recipients: Long-term hazard of severe infection is associated with long-term functional T cell impairment but not the ATG-induced CD4 cell decline.
abstract: METHODS
  We showed previously that rabbit ATG induction induces a strong decrease of CD4+ T cells together with impaired in vitro IL-2 secretion up to 1 year post-transplant. To further characterize long-term immunological effects of ATG induction 2 and 5 years post-transplant, we used sensitive intracellular cytokine analysis in the same prospective study of 84 renal transplant recipients (ATG, n=44).
  
  
  RESULTS
  A significantly increased frequency of severe infectious disease (HR=2.0, p=0.027) as well as suppressed T cell functions were found within 2 years after ATG induction but not beyond (logistic regression (logreg): CD4 cell IL-10 responses, p=0.064; T cell proliferation, p=0.038). Impaired T cell proliferation at 2 years was associated with occurrence of severe infection (p=0.017). Importantly, a strong and persistent decrease of CD4 cell counts (p<0.0005 at 5 years) was independently associated with ATG induction (logreg p=0.002) but not related to functional CD4 cell impairment (helper activity/cytokine production) or an increased risk of infection.
  
  
  CONCLUSIONS
  Severe infection up to 2 years after ATG induction was associated with impaired T cell proliferative capacity but not with the profound decline in CD4 cell counts that occurred after ATG induction and persisted up to 5 years.
authors: Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany. Electronic address: rolf.weimer@innere.med.uni-giessen.de.
authors: Rolf
authors: R
authors: Weimer
authors: Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany.
authors: Maryam
authors: M
authors: Ettrich
authors: Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany.
authors: Fabrice
authors: F
authors: Renner
authors: Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany.
authors: Hartmut
authors: H
authors: Dietrich
authors: Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany.
authors: Caner
authors: C
authors: Süsal
authors: Department of Internal Medicine, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany.
authors: Sabine
authors: S
authors: Deisz
authors: Department of Surgery, University of Giessen, Klinikstrasse 33, D-35385 Giessen, Germany.
authors: Winfried
authors: W
authors: Padberg
authors: Institute of Immunology, University of Heidelberg, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany.
authors: Gerhard
authors: G
authors: Opelz
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation; D003141:Communicable Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016753:Interleukin-10 / Q000276:immunology; D016030:Kidney Transplantation; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012720:Severity of Illness Index; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; C508609:IL10 protein, human; D007166:Immunosuppressive Agents; D016753:Interleukin-10