Appearance of cytomegalovirus-specific T-cells predicts fast resolution of viremia post hematopoietic stem cell transplantation
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26647177
DOI
10.1002/cyto.b.21348
Knihovny.cz E-resources
- Keywords
- T-cells, bone marrow transplantation, cytomegalovirus, flow cytometry, immune reconstitution,
- MeSH
- CD4-Positive T-Lymphocytes metabolism MeSH
- CD8-Positive T-Lymphocytes metabolism MeSH
- Cytomegalovirus Infections virology MeSH
- Cytomegalovirus metabolism MeSH
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Child, Preschool MeSH
- Flow Cytometry methods MeSH
- T-Lymphocyte Subsets immunology MeSH
- Hematopoietic Stem Cell Transplantation * methods MeSH
- Viremia metabolism MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Cytomegalovirus (CMV) specific T-cells are known to provide long-term control of CMV reactivation, which is a frequent complication of hematopoietic stem cell transplantation. We have studied 58 pediatric patients after hematopoietic stem cell transplantation who suffered from CMV reactivation to reveal which functional T cell subset is best correlating with successful reactivation resolution and which protects from reactivation episode. METHODS: Detection of 30 combinatorial subsets of four types of response to ex vivo CMV stimulation (IFNγ secretion, IL-2 secretion, CD40L upregulation and degranulation) that were detectable on either CD8+ or CD4+ T cells through flow cytometry intracellular cytokine staining was used. RESULTS: We found that the presence of CD8+ dual positive (IFNγ+ and IL-2+) cells is the most accurate functional parameter that can predict fast resolution of CMV reactivation. Next, we show that the presence of CD8+ dual positive (IFNγ+ and IL-2+) and CD8+ IFNγ+ cells provides a protective effect (a hazard risk of 0.28 (confidence interval 0.18 - 0.43) and 0.45 (CI 0.27 - 0.75), respectively) and the presence of corticotherapy increases the risk of reactivation (HR 2.47 (CI 1.82-3.36)). Thus, a patient without corticotherapy and with both of the critical T cell subsets present has a cumulative 19.6 times lower risk of developing CMV reactivation than a patient on corticotherapy and without CD8+ dual positive (IFNγ+ and IL-2+) or CD8+ IFNγ+ cells. CONCLUSIONS: We have established parameters of CMV specific functional response ex vivo that can be used in assisting clinical management of patients with CMV reactivation. © 2015 International Clinical Cytometry Society.
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