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Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT

Król, L. LU orcid ; Stuchl, J. ; Hubáek, P. ; Keslová, P. ; Sedláek, P. ; Star, J. ; Hruák, O. and Kalina, T. (2011) In Bone Marrow Transplantation 46(8). p.1089-1098
Abstract

Depletion of cellular immunity as a consequence of conditioning before allogeneic hematopoietic SCT (HSCT) frequently results in CMV reactivation, which may in turn lead to life-threatening infections and require timely antiviral treatment. We have investigated the functional signatures of CMV-specific CD4 and CD8+ T-cells in 191 samples from 118 individuals. We compared healthy donors with both patients with high and undetectable viral loads, and those who controlled and did not control their CMV reactivations. Polychromatic flow-cytometric measurements of CD154 (CD40L), intracellular cytokines (IFNγ, IL2) and a degranulation marker (CD107a) allowed us to assess the functional status of various T-cells simultaneously. We found that... (More)

Depletion of cellular immunity as a consequence of conditioning before allogeneic hematopoietic SCT (HSCT) frequently results in CMV reactivation, which may in turn lead to life-threatening infections and require timely antiviral treatment. We have investigated the functional signatures of CMV-specific CD4 and CD8+ T-cells in 191 samples from 118 individuals. We compared healthy donors with both patients with high and undetectable viral loads, and those who controlled and did not control their CMV reactivations. Polychromatic flow-cytometric measurements of CD154 (CD40L), intracellular cytokines (IFNγ, IL2) and a degranulation marker (CD107a) allowed us to assess the functional status of various T-cells simultaneously. We found that dual IFNγ/IL2-producing CD8+ T-cells were present in patients controlling their CMV reactivations but absent from non-controllers. CD8+ T-cells that produce only IFNγ were the most abundant subtype, but they most likely represent non-protective memory cells. Distinct functional signatures were examined by hierarchical clustering, and this revealed that, unlike polyfunctional CD8+ T-cells, CD8+ T-cells that produce IFNγ alone were not functioning in concert with other subsets. In conclusion, our study revealed functional signatures that may be useful for immune monitoring, and it could change the interpretation of previous studies that assessed only IFNγ.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
children, CMV, hematopoietic SCT, human T-cells, IFN-gamma, IL-2, immunologic monitoring
in
Bone Marrow Transplantation
volume
46
issue
8
pages
1089 - 1098
publisher
Nature Publishing Group
external identifiers
  • pmid:21057553
  • scopus:80051699900
ISSN
0268-3369
DOI
10.1038/bmt.2010.261
language
English
LU publication?
no
additional info
Funding Information: We thank D Thurner, D Kotus and L Gondorcinova for the technical assistance; V Kanderova for helpful discussions; the nurses of the Charles University 2nd Faculty of Medicine and University Hospital Motol HSCT unit, namely V Cepelakova, B Nagyova and A Pertlova, for handling patients samples; the physicians of the HSCT unit (R Formankova, M Matulova and A Stetsko) for outstanding patient care; M Zajac for serology testing; and K Kopecky and M Kopecka for collecting samples from healthy individuals. We thank all of our patients and healthy blood donors. The project was supported by Charles University Grant No. 47807, Ministry of Health of Czech Republic Grant No. NS/9996-4, MSMT21620813 and MZØFNM2005. Copyright: Copyright 2012 Elsevier B.V., All rights reserved.
id
f65bbe87-0988-48aa-a38b-8fef041bdba9
date added to LUP
2021-04-29 08:11:35
date last changed
2024-07-13 13:41:56
@article{f65bbe87-0988-48aa-a38b-8fef041bdba9,
  abstract     = {{<p>Depletion of cellular immunity as a consequence of conditioning before allogeneic hematopoietic SCT (HSCT) frequently results in CMV reactivation, which may in turn lead to life-threatening infections and require timely antiviral treatment. We have investigated the functional signatures of CMV-specific CD4 and CD8+ T-cells in 191 samples from 118 individuals. We compared healthy donors with both patients with high and undetectable viral loads, and those who controlled and did not control their CMV reactivations. Polychromatic flow-cytometric measurements of CD154 (CD40L), intracellular cytokines (IFNγ, IL2) and a degranulation marker (CD107a) allowed us to assess the functional status of various T-cells simultaneously. We found that dual IFNγ/IL2-producing CD8+ T-cells were present in patients controlling their CMV reactivations but absent from non-controllers. CD8+ T-cells that produce only IFNγ were the most abundant subtype, but they most likely represent non-protective memory cells. Distinct functional signatures were examined by hierarchical clustering, and this revealed that, unlike polyfunctional CD8+ T-cells, CD8+ T-cells that produce IFNγ alone were not functioning in concert with other subsets. In conclusion, our study revealed functional signatures that may be useful for immune monitoring, and it could change the interpretation of previous studies that assessed only IFNγ.</p>}},
  author       = {{Król, L. and Stuchl, J. and Hubáek, P. and Keslová, P. and Sedláek, P. and Star, J. and Hruák, O. and Kalina, T.}},
  issn         = {{0268-3369}},
  keywords     = {{children; CMV; hematopoietic SCT; human T-cells; IFN-gamma; IL-2; immunologic monitoring}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1089--1098}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Bone Marrow Transplantation}},
  title        = {{Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT}},
  url          = {{http://dx.doi.org/10.1038/bmt.2010.261}},
  doi          = {{10.1038/bmt.2010.261}},
  volume       = {{46}},
  year         = {{2011}},
}