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CMV-specific CD8(+) T-cell function is not impaired in chronic lymphocytic leukemia. / te Raa, G. Doreen; Pascutti, Maria Fernanda; García-Vallejo, Juan J. et al.

In: Blood, Vol. 123, No. 5, 2014, p. 717-724.

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te Raa, G. Doreen ; Pascutti, Maria Fernanda ; García-Vallejo, Juan J. et al. / CMV-specific CD8(+) T-cell function is not impaired in chronic lymphocytic leukemia. In: Blood. 2014 ; Vol. 123, No. 5. pp. 717-724.

BibTeX

@article{166de4bf3881439abf9023a9c6675dd0,
title = "CMV-specific CD8(+) T-cell function is not impaired in chronic lymphocytic leukemia",
abstract = "In chronic lymphocytic leukemia (CLL), CD8(+) T cells exhibit features of exhaustion and impaired functionality. Yet, reactivations of latent viruses such as cytomegalovirus (CMV) are uncommon in untreated CLL, suggesting that antiviral responses are uncompromised. We analyzed phenotypical and functional characteristics of CMV-specific CD8(+) T cells in CLL patients in comparison with age-matched healthy controls (HCs). Despite increased expression of the inhibitory receptors PD1, CD160, and CD244 on total CD8(+) T cells in CLL, expression levels of these markers were decreased on CMV-tetramer(+)CD8(+) T cells. Second, cytokine production upon stimulation with both phorbol 12-myristate 13-acetate/ionomycin and CMV-peptide-loaded antigen-presenting cells was intact in CMV-tetramer(+)CD8(+) T cells. Third, CMV-tetramer(+)CD8(+) T cells of CLL patients and HCs were equally effective in killing CMV-peptide-loaded target cells. Finally, quantitative imaging flow cytometry revealed that the proportion of CD8(+) T cells forming immunologic synapses with CMV-peptide-loaded B cells was intact. In conclusion, despite evidence for global T-cell dysfunction in CLL, we show here that CLL-derived CMV-specific CD8(+) T cells display lower expression of exhaustion markers and are functionally intact. These data indicate that the changes in the T-cell compartment in CLL may be more heterogeneous than presently assumed",
author = "{te Raa}, {G. Doreen} and Pascutti, {Maria Fernanda} and Garc{\'i}a-Vallejo, {Juan J.} and Emilie Reinen and Remmerswaal, {Ester B. M.} and {ten Berge}, {Ineke J. M.} and {van Lier}, {Ren{\'e} A. W.} and Eric Eldering and {van Oers}, {Marinus H. J.} and Tonino, {Sanne H.} and Kater, {Arnon P.}",
year = "2014",
doi = "10.1182/blood-2013-08-518183",
language = "English",
volume = "123",
pages = "717--724",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "5",

}

RIS

TY - JOUR

T1 - CMV-specific CD8(+) T-cell function is not impaired in chronic lymphocytic leukemia

AU - te Raa, G. Doreen

AU - Pascutti, Maria Fernanda

AU - García-Vallejo, Juan J.

AU - Reinen, Emilie

AU - Remmerswaal, Ester B. M.

AU - ten Berge, Ineke J. M.

AU - van Lier, René A. W.

AU - Eldering, Eric

AU - van Oers, Marinus H. J.

AU - Tonino, Sanne H.

AU - Kater, Arnon P.

PY - 2014

Y1 - 2014

N2 - In chronic lymphocytic leukemia (CLL), CD8(+) T cells exhibit features of exhaustion and impaired functionality. Yet, reactivations of latent viruses such as cytomegalovirus (CMV) are uncommon in untreated CLL, suggesting that antiviral responses are uncompromised. We analyzed phenotypical and functional characteristics of CMV-specific CD8(+) T cells in CLL patients in comparison with age-matched healthy controls (HCs). Despite increased expression of the inhibitory receptors PD1, CD160, and CD244 on total CD8(+) T cells in CLL, expression levels of these markers were decreased on CMV-tetramer(+)CD8(+) T cells. Second, cytokine production upon stimulation with both phorbol 12-myristate 13-acetate/ionomycin and CMV-peptide-loaded antigen-presenting cells was intact in CMV-tetramer(+)CD8(+) T cells. Third, CMV-tetramer(+)CD8(+) T cells of CLL patients and HCs were equally effective in killing CMV-peptide-loaded target cells. Finally, quantitative imaging flow cytometry revealed that the proportion of CD8(+) T cells forming immunologic synapses with CMV-peptide-loaded B cells was intact. In conclusion, despite evidence for global T-cell dysfunction in CLL, we show here that CLL-derived CMV-specific CD8(+) T cells display lower expression of exhaustion markers and are functionally intact. These data indicate that the changes in the T-cell compartment in CLL may be more heterogeneous than presently assumed

AB - In chronic lymphocytic leukemia (CLL), CD8(+) T cells exhibit features of exhaustion and impaired functionality. Yet, reactivations of latent viruses such as cytomegalovirus (CMV) are uncommon in untreated CLL, suggesting that antiviral responses are uncompromised. We analyzed phenotypical and functional characteristics of CMV-specific CD8(+) T cells in CLL patients in comparison with age-matched healthy controls (HCs). Despite increased expression of the inhibitory receptors PD1, CD160, and CD244 on total CD8(+) T cells in CLL, expression levels of these markers were decreased on CMV-tetramer(+)CD8(+) T cells. Second, cytokine production upon stimulation with both phorbol 12-myristate 13-acetate/ionomycin and CMV-peptide-loaded antigen-presenting cells was intact in CMV-tetramer(+)CD8(+) T cells. Third, CMV-tetramer(+)CD8(+) T cells of CLL patients and HCs were equally effective in killing CMV-peptide-loaded target cells. Finally, quantitative imaging flow cytometry revealed that the proportion of CD8(+) T cells forming immunologic synapses with CMV-peptide-loaded B cells was intact. In conclusion, despite evidence for global T-cell dysfunction in CLL, we show here that CLL-derived CMV-specific CD8(+) T cells display lower expression of exhaustion markers and are functionally intact. These data indicate that the changes in the T-cell compartment in CLL may be more heterogeneous than presently assumed

U2 - 10.1182/blood-2013-08-518183

DO - 10.1182/blood-2013-08-518183

M3 - Article

C2 - 24246502

VL - 123

SP - 717

EP - 724

JO - Blood

JF - Blood

SN - 0006-4971

IS - 5

ER -

ID: 2247429