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

Background and 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.

Trial registration: ClinicalTrials.gov NCT00150891.