Rapid reconstitution of <scp>CMV</scp>‐specific T‐cells after stem‐cell transplantation

Widmann, Thomas; Sester, Urban; Schmidt, Tina; Гартнер, Барбара; Schubert, Jörg; Pfreundschuh, Michael; Sester, Martina

doi:10.1111/ejh.13077

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…PBMCs (3 * 10 6 cells/ml) were seeded into 48‐well cell culture plates (7.5 * 10 5 cells/well) at 37°C. Afterwards, PBMCs were stimulated with the major target antigens of CMV‐specific peptide mix (1 μg/ml) consisting of pool of Pp65 + IE1 peptides (ELSP5944, AID, Germany) as previously described [9,22,23], withCD3/CD28 (100 ng/ml) (eBioscience clones OKT3, CD28.2) as a positive control, or with IL‐2 (100 ng/ml) (BD Biosciences, Heidelberg, Germany). Simultaneously, CMV‐ and CD3/CD28‐stimulated cells were cultured for 24 h or 7 days in a humidified atmosphere of 5% CO 2 at 37°C to determine pSTAT5A and T cell proliferation, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…In healthy CMV‐infected individuals, pathogenesis is controlled by CMV‐specific T cells involving both CD4 + and CD8 + T cells. Loss or suppression of adaptive immunity as accrues in primary and secondary immune deficiencies, transplant patients, or older people who suffer from age‐associated changes in the immune system frequently leads to CMV reactivation [2–11].…”

Section: Introductionmentioning

confidence: 99%

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Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus‐stimulated T cells

et al. 2020

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Cytomegalovirus (CMV)‐specific T cells expand with CMV reactivation and are probably prerequisite for control and protection. Given the critical role STAT5A phosphorylation (pSTAT5A) in T cell proliferation, this study presents a simple and sensitive flow cytometric‐based pSTAT5A assay to quickly identify CMV‐specific T cell proliferation. We determined pSTAT5A in T cells treated with CMV‐specific peptide mix (pp65 + IE1 peptides) from 20 healthy adult subjects and three immunodeficient patients with CARMIL‐2 mutation. After stimulation, the percentage of pSTAT5A+ T cells in CMV‐seropositive (CMV+) subjects significantly increased from 3.0% ± 1.9% (unstimulated) to 11.4% ± 5.9% (stimulated) for 24 h. After 7 days of stimulation, the percentage of expanded T cells amounted to 26% ± 17.2%. Conversely, the percentage of pSTAT5A+ T cells and T cell proliferation from CMV‐seronegative (CMV−) subjects hardly changed (from 3.0% ± 1.3% to 3.7% ± 1.8% and from 4.3% ± 2.1% to 5.7% ± 1.7%, respectively). We analyzed the correlation between the percentage of pSTAT5A+ T cells versus (1) CMV‐IgG concentrations versus (2) the percentage of expanded T cells and versus (3) the percentage of initial CMV‐specific T cells. In immunodeficient patients with CARMIL‐2 mutation, CMV‐specific pSTAT5A and T cell proliferation were completely deficient. In conclusion, flow cytometric‐based pSTAT5A assay represents an appropriate tool to quickly identify CMV‐specific T cell proliferation and helps to understand dysfunctions in controlling other pathogens. Flow cytometric‐based pSTAT5A assay may be a useful test in clinical practice and merits further validation in large studies.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus‐stimulated T cells

et al. 2020

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Prevention and treatment of cytomegalovirus in immunocompromised patients: beyond DNA polymerase inhibition

Montoya

Gómez

Lee³

2018

Current Opinion in Infectious Diseases

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Cytomegalovirus-specific T cell immunity reconstitution following allogeneic hematopoietic stem cell transplantation: a pilot stduy

Wang,

Li,

Huang

et al. 2023

Preprint

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Purpose Reactivation of cytomegalovirus (CMV) leads to significant morbidity and mortality following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The reconstitution of CMV-specific T cells plays a crucial role in the antiviral response after allo-HSCT. However, the impact of CMV reactivation on the recovery of CMV-specific T cells in the early stages after allo-HSCT, particularly haploidentical HSCT, remains undisclosed. Methods We retrospectively examined CMV-specific T-cell recovery in 78 allo-HSCT recipients to assess the influence of clinically significant CMV infection (CS-CMVi) on CMV-specific T-cell restoration. Results Patients in CS-CMVi group displayed higher absolute quantities of CMV-specific IFN-γ+ T cells on day 30 (CD4+ T cells: 1.40 vs. 0.07 cells/µL, p = 0.02; CD8+ T cells: 1.64 vs. 0.15 cells/µL, p = 0.11), but lower counts on day 180 (CD4+ T cells: 1.06 vs. 5.95 cells/µL, p < 0.01; CD8+ T cells: 3.70 vs. 55.36 cells/µL, p = 0.04). Among patients receiving letermovir prophylaxis (LTV group), the recovery of CMV-specific CD8+ T cells was significantly delayed compared to those receiving preemptive therapy (PET group) from day 60. The LTV group was more likely to experience late-onset CMV reactivation if their absolute counts of polyfunctional CMV-specific CD4+ T cells or CD8+ T cells was below 2.01 (AUC = 0.78, p = 0.003) or 0.90 cells/µL (AUC = 0.89, p < 0.001). Conclusions In conclusion, our pilot study provides direct evidence that early episodes of CS-CMVi impair the recovery of CMV-specific T cells after allo-HSCT. Additionally, insufficient polyfunctional restoration would lead to late-onset CMV reactivation in LTV group.

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Rapid reconstitution of CMV‐specific T‐cells after stem‐cell transplantation

Abstract: Cytomegalovirus-specific T-cells rapidly reconstitute after SCT and their percentages remain high in the long term. In the face of persistent lymphopenia, this results in similar absolute numbers of CMV-specific T-cells as in controls to ensure sufficient pathogen control.

Cited by 4 publications

References 39 publications

Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus‐stimulated T cells

Flow cytometric measurement of STAT5 phosphorylation in cytomegalovirus‐stimulated T cells

Prevention and treatment of cytomegalovirus in immunocompromised patients: beyond DNA polymerase inhibition

Cytomegalovirus-specific T cell immunity reconstitution following allogeneic hematopoietic stem cell transplantation: a pilot stduy

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