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Reconstitution of cytomegalovirus specific T cells after pediatric allogeneic stem cell transplantation: results from a pilot study using a multi-allele CMV tetramer group.
Klin Padiatr. 2008 Nov-Dec; 220(6):348-52.KP

Abstract

BACKGROUND

Recovery of cytomegalovirus (CMV)-specific T cell mediated immunity after allogeneic hematopoietic stem cell transplantation (SCT) is critical for protection against CMV disease. Tetramer-based technologies have been shown to be a sensitive tool in the enumeration of specific T cells, but have the disadvantage of HLA-restriction of the peptides.

PATIENTS AND METHODS

In this pilot study, we tested the feasibility of a panel of 6 CMV-specific tetrameric HLA/CMV-peptide complexes to enumerate CMV-specific CD8 +T cells (CTLs). The reconstitution of CMV-specific CTLs was assessed in 16 children in the first year after allogeneic SCT (median age, 8 years).

RESULTS

The presented assay covered more than 85% of our patients transplanted in the last 3 years. During CMV-reactivation, all 4 of the 16 analyzed patients with a high virus-load showed less than 10 CMV-specific CTLs/microl; out of these, three had not any detectable CMV-CTLs. On the other hand, five of the children with less than 10 CMV-specific CTLs/microl did not develop CMV reactivation. When enumeration of T cells was performed by means of different tetrameric HLA/CMV-peptide complexes simultaneously, the numbers of CMV-specific CTLs cells widely differed according to the HLA-type.

CONCLUSIONS

Our pilot study suggests that enumeration of CMV-specific T cells by means of a panel of 6 tetramers might be a useful tool in the risk assessment for CMV reactivation in the majority of patients undergoing allogeneic SCT, but future trials have to evaluate whether this method is appropriate in tailoring antiviral therapy in the individual patient.

Authors+Show Affiliations

Pediatric Hematology and Oncology, University Children's Hospital, Frankfurt/Main, Germany. Ulrike.Koehl@kgu.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18949669

Citation

Koehl, U, et al. "Reconstitution of Cytomegalovirus Specific T Cells After Pediatric Allogeneic Stem Cell Transplantation: Results From a Pilot Study Using a Multi-allele CMV Tetramer Group." Klinische Padiatrie, vol. 220, no. 6, 2008, pp. 348-52.
Koehl U, Dirkwinkel E, Koenig M, et al. Reconstitution of cytomegalovirus specific T cells after pediatric allogeneic stem cell transplantation: results from a pilot study using a multi-allele CMV tetramer group. Klin Padiatr. 2008;220(6):348-52.
Koehl, U., Dirkwinkel, E., Koenig, M., Erben, S., Soerensen, J., Bader, P., Doerr, H. W., Preiser, W., Weissinger, E., Klingebiel, T., Martin, H., & Lehrnbecher, T. (2008). Reconstitution of cytomegalovirus specific T cells after pediatric allogeneic stem cell transplantation: results from a pilot study using a multi-allele CMV tetramer group. Klinische Padiatrie, 220(6), 348-52. https://doi.org/10.1055/s-0028-1086029
Koehl U, et al. Reconstitution of Cytomegalovirus Specific T Cells After Pediatric Allogeneic Stem Cell Transplantation: Results From a Pilot Study Using a Multi-allele CMV Tetramer Group. Klin Padiatr. 2008 Nov-Dec;220(6):348-52. PubMed PMID: 18949669.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reconstitution of cytomegalovirus specific T cells after pediatric allogeneic stem cell transplantation: results from a pilot study using a multi-allele CMV tetramer group. AU - Koehl,U, AU - Dirkwinkel,E, AU - Koenig,M, AU - Erben,S, AU - Soerensen,J, AU - Bader,P, AU - Doerr,H W, AU - Preiser,W, AU - Weissinger,E, AU - Klingebiel,T, AU - Martin,H, AU - Lehrnbecher,T, Y1 - 2008/10/23/ PY - 2008/10/25/pubmed PY - 2009/1/13/medline PY - 2008/10/25/entrez SP - 348 EP - 52 JF - Klinische Padiatrie JO - Klin Padiatr VL - 220 IS - 6 N2 - BACKGROUND: Recovery of cytomegalovirus (CMV)-specific T cell mediated immunity after allogeneic hematopoietic stem cell transplantation (SCT) is critical for protection against CMV disease. Tetramer-based technologies have been shown to be a sensitive tool in the enumeration of specific T cells, but have the disadvantage of HLA-restriction of the peptides. PATIENTS AND METHODS: In this pilot study, we tested the feasibility of a panel of 6 CMV-specific tetrameric HLA/CMV-peptide complexes to enumerate CMV-specific CD8 +T cells (CTLs). The reconstitution of CMV-specific CTLs was assessed in 16 children in the first year after allogeneic SCT (median age, 8 years). RESULTS: The presented assay covered more than 85% of our patients transplanted in the last 3 years. During CMV-reactivation, all 4 of the 16 analyzed patients with a high virus-load showed less than 10 CMV-specific CTLs/microl; out of these, three had not any detectable CMV-CTLs. On the other hand, five of the children with less than 10 CMV-specific CTLs/microl did not develop CMV reactivation. When enumeration of T cells was performed by means of different tetrameric HLA/CMV-peptide complexes simultaneously, the numbers of CMV-specific CTLs cells widely differed according to the HLA-type. CONCLUSIONS: Our pilot study suggests that enumeration of CMV-specific T cells by means of a panel of 6 tetramers might be a useful tool in the risk assessment for CMV reactivation in the majority of patients undergoing allogeneic SCT, but future trials have to evaluate whether this method is appropriate in tailoring antiviral therapy in the individual patient. SN - 0300-8630 UR - https://www.unboundmedicine.com/medline/citation/18949669/Reconstitution_of_cytomegalovirus_specific_T_cells_after_pediatric_allogeneic_stem_cell_transplantation:_results_from_a_pilot_study_using_a_multi_allele_CMV_tetramer_group_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-0028-1086029 DB - PRIME DP - Unbound Medicine ER -