Allospecific CD154+ T Cells Associate with Rejection Risk After Pediatric Liver Transplantation
| Autor: | Chethan Ashokkumar, Jennifer Dobberstein, Ronald Jaffe, Brandon W. Higgs, Geoffrey Bond, Rakesh Sindhi, Kyle Soltys, Anjan Talukdar, George V. Mazariegos, Adriana Zeevi, Patrick Wilson, Qing Sun, Anthony J. Demetris, Angus W. Thomson, Janine E. Janosky |
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| Rok vydání: | 2009 |
| Předmět: |
Graft Rejection
Male T-Lymphocytes medicine.medical_treatment CD40 Ligand chemical and pharmacologic phenomena Liver transplantation Article Flow cytometry Cohort Studies Antigens CD medicine Humans Immunology and Allergy Cytotoxic T cell CTLA-4 Antigen Pharmacology (medical) CD154 Child Transplantation CD40 biology medicine.diagnostic_test business.industry Incidence (epidemiology) Alloimmunity hemic and immune systems Tacrolimus Liver Transplantation surgical procedures operative Child Preschool Immunology biology.protein Female business Immunologic Memory |
| Zdroj: | American Journal of Transplantation. 9:179-191 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/j.1600-6143.2008.02459.x |
| Popis: | Antigen-specific T cells, which express CD154 rapidly, but remain untested in alloimmunity, were measured with flow cytometry in 16-h MLR of 58 identically-immunosuppressed children with liver transplantation (LTx), to identify Rejectors (who had experienced biopsy-proven rejection within 60 days posttransplantation). Thirty-one children were sampled once, cross-sectionally. Twenty-seven children were sampled longitudinally, pre-LTx, and at 1-60 and 61-200 days after LTx. Results were correlated with proliferative alloresponses measured by CFSE-dye dilution (n = 23), and CTLA4, a negative T-cell costimulator, which antagonizes CD154-mediated effects (n = 31). In cross-sectional observations, logistic regression and leave-one-out cross-validation identified donor-specific, CD154 + T-cytotoxic (Tc)-memory cells as best associated with rejection outcomes. In the longitudinal cohort, (1) the association between CD154 + Tc-memory cells and rejection outcomes was replicated with sensitivity/specificity 92.3%/84.6% for observations at 1-60 days, and (2) elevated pre-LTx CD154 + Tc-memory cell responses were associated with significantly increased incidence (p = 0.02) and hazard (HR = 7.355) of rejection in survival/proportional hazard analysis. CD154 expression correlated with proliferative alloresponses (r = 0.835, p = 7.1e-07), and inversely with CTLA4 expression of allospecific CD154 + Tc-memory cells (r =-0.706, p = 3.0e-05). Allospecific CD154 + T-helper-memory cells, not CD154 + Tc-memory, were inhibited by increasing Tacrolimus concentrations (p = 0.026). Collectively, allospecific CD154 + T cells provide an estimate of rejection risk in children with LTx. |
| Databáze: | OpenAIRE |
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