T-cell suppression through induction therapy is routinely used to promote graft survival in high immunological risk (HR) and donation after cardiac death (DCD) renal transplant recipients. Depletional therapy with anti-thymocyte globulin (ATG) initially leads to lymphopenia. The immune system however, has the capacity to repopulate the T-cell compartment. The T-cell response post ATG induction has not been characterized in HR and DCD recipients, who often have increased rates of rejection despite adequate immune suppression. Understanding this response is critical for optimizing early immune therapies.
To establish the dynamics of T-cell reconstitution in DCD and HR recipients after ATG induction.
Reconstitution and proliferation rates of recipient (HR n=10 and DCD n=10) T-cell subsets were analyzed by 13-colour flow cytometry for 6 months post induction therapy with ATG. Following ATG, there was a rapid decline in the frequency of T-cells in both groups. Levels remained depressed for over 28 d. In HR patients, there was a rapid surge in the frequency of CD4 naive T-cells, which was not observed in DCD recipients. Although we observed significant proliferation in the effector memory phenotype in both HR and DCD patients, the response in the DCD cohort was blunted. Regulatory T-cells showed a surge in proliferation rates, however the magnitude of change was not as great in the DCD group. Immune reactivity, assessed using the ImmuKnow® assay, revealed CD4 T-lymphocytes were less immune-reactive in the DCD group.
This preliminary study provides perspective on the effects of ATG on the T cell response at an early period following renal transplantation in two important and rapidly growing populations of recipients (HR and DCD). Initial data suggests there is a lack of significant homeostatic proliferative response in DCD recipients following ATG. Moreover, data suggests that CD4-lymphocytes may be less reactive in the DCD group. These observations suggest that ATG may be an overly aggressive approach in DCD recipients.
To cite this abstract in AMA style:Telfer S, Ullah S, Fear T, Mok A, Jevnikar A, Luke P, Sener A. Dichotomous T-Cell Repopulation after Anti-Thymocyte Globulin Induction Therapy in High Immunological Risk and DCD Renal Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/dichotomous-t-cell-repopulation-after-anti-thymocyte-globulin-induction-therapy-in-high-immunological-risk-and-dcd-renal-transplant-recipients/. Accessed August 11, 2020.
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