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Enhanced Donor‐Specific Alloreactivity Occurs Independently of Immunosuppression in Children with Early Liver Rejection
Author(s) -
Sindhi Rakesh,
Magill Amy,
Bentlejewski Carol,
Abdullah Ali,
Tresgaskes Mary,
Seward Joseph,
Janosky Janine,
Zeevi Adriana
Publication year - 2005
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00639.x
Subject(s) - immunosuppression , medicine , cd8 , immunology , population , cytotoxic t cell , immune system , mixed lymphocyte reaction , liver transplantation , antigen , tacrolimus , lymphocyte , transplantation , t cell , in vitro , biology , biochemistry , environmental health
To determine whether early acute cellular rejection (ACR) is associated with sub‐optimal immunosuppression in children with liver transplants (LTx). Methods: Twenty‐five children with primary LTx after pre‐transplant rabbit anti‐thymocyte globulin (rATG), and steroid‐free tacrolimus (TAC) were evaluated. Mitogen‐stimulated T‐ and B‐cell responses and mixed lymphocyte response to donor and third‐party antigens were performed at several time points between two consecutive TAC doses. TAC concentrations (C) associated with half‐maximal effect (EC 50 ) on lymphocytes was determined by pharmacodynamic equations. Results: Mean age was 7.2 ± 6.2 years, mean time to lymphocyte function studies was 25 ± 19 days. Acute rejection occurred at a mean interval of 31 ± 19 days after LTx. Rejectors (n = 16) demonstrated significantly higher EC 50 of TAC for the intra‐cellular IFN‐γ in T cells (p = 0.005) and its CD8+ sub‐population (p = 0.027) as well as the co‐stimulatory/activation receptor CD54 on B cells (p = 0.0001). The response of recipient lymphocytes to donor antigen was significantly higher in rejectors, compared with non‐rejectors (p = 0.015). The patient groups demonstrated no differences in third‐party MLR, or in C of TAC. Conclusions: Independent of the amount of immunosuppressant, ACR of liver allografts in children is associated with enhanced donor‐specific alloreactivity. This is accompanied by a cytotoxic T‐cell sub‐population with increased requirement for TAC.