Appearance of cytomegalovirus-specific T-cells predicts fast resolution of viremia post hematopoietic stem cell transplantation
Pelák, Ondřej ; Stuchlý, Jan ; Król, Ladislav LU
; Hubáček, Petr
; Keslová, Petra
; Sedláček, Petr
; Formánková, Renata
; Starý, Jan
; Hrušák, Ondřej
and Kalina, Tomáš
(2017)
In Cytometry Part B - Clinical Cytometry
92(5).
p.380-388
- Abstract
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... (More)
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.
(Less)
- author
- Pelák, Ondřej
; Stuchlý, Jan
; Król, Ladislav
LU
; Hubáček, Petr
; Keslová, Petra
; Sedláček, Petr
; Formánková, Renata
; Starý, Jan
; Hrušák, Ondřej
and Kalina, Tomáš
- publishing date
- 2017-09
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- bone marrow transplantation, cytomegalovirus, flow cytometry, immune reconstitution, T-cells
- in
- Cytometry Part B - Clinical Cytometry
- volume
- 92
- issue
- 5
- pages
- 380 - 388
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85040368991
- pmid:26647177
- ISSN
- 1552-4949
- DOI
- 10.1002/cyto.b.21348
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2015 International Clinical Cytometry Society. Copyright: This record is sourced from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
- id
- 3ff870be-e639-473a-bab4-bb772f31c57a
- date added to LUP
- 2021-04-29 08:08:54
- date last changed
- 2024-06-02 13:17:57
@article{3ff870be-e639-473a-bab4-bb772f31c57a,
abstract = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
author = {{Pelák, Ondřej and Stuchlý, Jan and Król, Ladislav and Hubáček, Petr and Keslová, Petra and Sedláček, Petr and Formánková, Renata and Starý, Jan and Hrušák, Ondřej and Kalina, Tomáš}},
issn = {{1552-4949}},
keywords = {{bone marrow transplantation; cytomegalovirus; flow cytometry; immune reconstitution; T-cells}},
language = {{eng}},
number = {{5}},
pages = {{380--388}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Cytometry Part B - Clinical Cytometry}},
title = {{Appearance of cytomegalovirus-specific T-cells predicts fast resolution of viremia post hematopoietic stem cell transplantation}},
url = {{http://dx.doi.org/10.1002/cyto.b.21348}},
doi = {{10.1002/cyto.b.21348}},
volume = {{92}},
year = {{2017}},
}