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Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients

Egli, A. and Binet, I. and Binggeli, S. and Jäger, C. and Dumoulin, A. and Schaub, S. and Steiger, J. and Sester, U. and Sester, M. and Hirsch, H. H.. (2008) Cytomegalovirus-specific T-cell responses and viral replication in kidney transplant recipients. Journal of translational medicine, Vol. 6. p. 29.

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Official URL: http://edoc.unibas.ch/dok/A6006592

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Abstract

BACKGROUND: Cytomegalovirus (CMV) seronegative recipients (R-) of kidney transplants (KT) from seropositive donors (D+) are at higher risk for CMV replication and ganciclovir(GCV)-resistance than CMV R(+). We hypothesized that low CMV-specific T-cell responses are associated with increased risk of CMV replication in R(+)-patients with D(+) or D(-) donors. METHODS: We prospectively evaluated 73 consecutive KT-patients [48 R(+), 25 D(+)R(-)] undergoing routine testing for CMV replication as part of a preemptive strategy. We compared CMV-specific interferon-gamma (IFN-gamma) responses of CD4+CD3+ lymphocytes in peripheral blood mononuclear cells (PBMC) using three different antigen preparation (CMV-lysate, pp72- and pp65-overlapping peptide pools) using intracellular cytokine staining and flow cytometry. RESULTS: Median CD4+ and CD8+T-cell responses to CMV-lysate, pp72- and pp65-overlapping peptide pools were lower in D(+)R(-) than in R(+)patients or in non-immunosuppressed donors. Comparing subpopulations we found that CMV-lysate favored CD4+- over CD8+-responses, whereas the reverse was observed for pp72, while pp65-CD4+- and -CD8+-responses were similar. Concurrent CMV replication in R(+)-patients was associated with significantly lower T-cell responses (pp65 median CD4+ 0.00% vs. 0.03%, p = 0.001; CD8+ 0.01% vs. 0.03%; p = 0.033). Receiver operated curve analysis associated CMV-pp65 CD4+ responses of < 0.03% in R(+)-patients with absence of concurrent (p = 0.003) and future CMV replication in the following 8 weeks (p = 0.036). GCV-resistant CMV replication occurred in 3 R(+)-patients (6.3%) with pp65- CD4+ frequencies > 0.03% (p = 0.041). CONCLUSION: The data suggest that pp65-specific CD4+ T-cells might be useful to identify R(+)-patients at increased risk of CMV replication. Provided further corroborating evidence, CMV-pp65 CD4+ responses above 0.03% in PBMCs of KT patients under stable immunosuppression are associated with lower risk of concurrent and fut CMV replication during the following 8 weeks.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Nephrologie > Transplantationsimmunologie und Nephrologie (Steiger)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Nephrologie > Transplantationsimmunologie und Nephrologie (Steiger)
03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Transplantation Virology (Hirsch)
03 Faculty of Medicine > Departement Biomedizin > Former Units at DBM > Transplantation Immunology and Nephrology (Palmer/Steiger)
UniBasel Contributors:Schaub, Stefan and Steiger, Jürg U. and Hirsch, Hans H.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:BioMed Central
ISSN:1479-5876
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Apr 2014 08:00
Deposited On:25 Apr 2014 08:00

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