Signature profiles of CMV-specific T-cells in patients with CMV reactivation after hematopoietic SCT
(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
- Król, L. LU ; Stuchl, J. ; Hubáek, P. ; Keslová, P. ; Sedláek, P. ; Star, J. ; Hruák, O. and Kalina, T.
- publishing date
- 2011-08
- 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
-
- scopus:80051699900
- pmid:21057553
- 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}}, }