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

Krol, Laurie Vande; Stuchlý, Jan; Hubáček, Petr; Keslová, Petra; Sedláček, Petr; Starý, Jan; Hrušák, Ondřej; Kalina, Tomáš

doi:10.1038/bmt.2010.261

Cited by 44 publications

(45 citation statements)

References 47 publications

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“…Our findings are consistent, however, with a prior study by Lilleri et al who also found that polyfunctional CMV-specific T cells producing IFNγ and IL-2 were associated with protection (43). In addition, the increase of MFI values of IFNγ with decreased CMV-specific CD8 + polyfunctionality in PBSC recipients at day 30, aligns with the work of Krol et al, who suggested that production of IFNγ alone may be a sign of T cell exhaustion during viral infection (44). We recently showed, using CMV-specific tetramers, that HCT patients with ≥ 7 positive tetramer cells per mL in at least one blood sample before day 65 post-transplant were statistically protected from CMV infection (45), although the protection was not complete.…”

Section: Discussionsupporting

confidence: 86%

Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

Guerrero

Riddell

Storek

et al. 2012

Biology of Blood and Marrow Transplantation

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Peripheral blood stem cell (PBSC) products contain more T cells and monocytes when compared to bone marrow (BM), leading to fewer bacterial and fungal infections. CMV viral load and disease as well as CMV-specific immune reconstitution were compared in patients enrolled in a randomized trial comparing PSBC and BM transplantation. There was a higher rate of CMV infection and disease during the first 100 days after transplantation among PBSC recipients (any antigenemia/DNAemia: PBSC, 63% vs. BM, 42%, P=0.04; CMV disease: PBSC, 17% vs. BM, 4%, P=0.03). By two years, CMV disease rates were similar. The early increase in CMV events correlated temporarily with lower CMV-specific CD4+ T helper and CD8+ cytotoxic T lymphocyte function at 30 days after transplantation in PBSC recipients. By 3 months after transplantation and thereafter, CMV-specific immune responses were similar between BM and PBSC recipients. In conclusion, higher CMV infection and disease rates occurred in PBSC transplant recipients early after transplantation. These differences may be due to a transient delay in CMV specific immune reconstitution following PBSC transplantation.

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Section: Discussionsupporting

confidence: 86%

Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

Guerrero

Riddell

Storek

et al. 2012

Biology of Blood and Marrow Transplantation

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“…All analyzed CVID-AcT patients presented detectable levels of a CMV IL-10 homolog, which was concordant with the presence of a CMV-specific T-cell response (data not shown). CMV persistence was confirmed in 8 out of 9 CVID-AcT patients and in 11 out of 15 other CVID patients by intracellular cytokine staining after CMV peptide stimulation, as described previously3233.…”

Section: Resultsmentioning

confidence: 99%

Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

Stuchlý

Kanderová

Vlková

et al. 2017

Sci Rep

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Common variable immunodeficiency (CVID) is a heterogeneous group of diseases. Our aim was to define sub-groups of CVID patients with similar phenotypes and clinical characteristics. Using eight-color flow cytometry, we analyzed both B- and T-cell phenotypes in a cohort of 88 CVID patients and 48 healthy donors. A hierarchical clustering of probability binning “bins” yielded a separate cluster of 22 CVID patients with an abnormal phenotype. We showed coordinated proportional changes in naïve CD4+ T-cells (decreased), intermediate CD27− CD28+ CD4+ T-cells (increased) and CD21low B-cells (increased) that were stable for over three years. Moreover, the lymphocytes’ immunophenotype in this patient cluster exhibited features of profound immunosenescence and chronic activation. Thrombocytopenia was only found in this cluster (36% of cases, manifested as Immune Thrombocytopenia (ITP) or Evans syndrome). Clinical complications more frequently found in these patients include lung fibrosis (in 59% of cases) and bronchiectasis (55%). The degree of severity of these symptoms corresponded to more deviation from normal levels with respect to CD21low B-cells, naïve CD4+ and CD27− CD28+ over three years. Moreover, th-cells. Next-generation sequencing did not reveal any common genetic background. We delineate a subgroup of CVID patients with activated and immunosenescent immunophenotype of lymphocytes and distinct set of clinical complications without common genetic background.

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“…Polyfunctional T cells, capable of the simultaneous production of multiple cytokines, have been associated with improved immunological control across many acute and chronic viral infections, including CMV (Betts et al 2006;Darrah et al 2007;Krol et al 2011;Sauce et al 2016). Recently, Chiu et al described that a higher degree of cytotoxicity-associated polyfunctionality was positively correlated with a larger total CMV-specific response size, both for CD8+ and CD4+ CMV responses (Chiu et al 2016).…”

Section: T Cell Polyfunctionality and CMV Responsesmentioning

confidence: 99%

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

Souquette¹,

Frere²,

Smithey³

et al. 2017

GeroScience

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Approximately 50% of individuals aged 6-49 years in the United States are infected with cytomegalovirus (CMV), with seroprevalence increasing with age, reaching 85-90% by 75-80 years according to Bate et al. (Clin Infect Dis 50 (11): 1439-1447 and Pawelec et al. (Curr Opin Immunol 24:507-511, 2012). Following primary infection, CMV establishes lifelong latency with periodic reactivation. Immunocompetent hosts experience largely asymptomatic infection, but CMV can cause serious illness in immunocompromised populations, such as transplant patients and the elderly. Control of CMV requires constant immune surveillance, and recent discoveries suggest this demand alters general features of the immune system in infected individuals. Here, we review recent advances in the understanding of the immune response to CMV and the role of CMV in immune aging and fitness, while highlighting the importance of potential confounding factors that influence CMV studies. Understanding how CMV contributes to shaping Bbaseline^immunity has important implications for a host's ability to mount effective responses to diverse infections and vaccination.

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

Cited by 44 publications

References 47 publications

Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

Common Variable Immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia

A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness

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