The peripheral helper T-cell repertoire in untreated indolent B-cell lymphomas: evidence for antigen-driven lymphomagenesis

Christopoulos, Petros; Follo, Marie; Fisch, Paul; Veelken, Hendrik

doi:10.1038/leu.2008.82

Cited by 11 publications

(11 citation statements)

References 9 publications

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“…Whereas specific TCR repertoire patterns have now been demonstrated in different hematologic and extra‐hematologic malignancies , the few studies exploring the T‐cell compartment of patients with B‐cell NHL just point to an overall activation of the TCR repertoire and are extremely heterogeneous in terms of methodological approach and disease subtype . The only available spectratyping analysis was performed on unseparated peripheral T cells and showed a restricted TCR repertoire in marginal zone mucosa‐associated lymphoid tissue (MALT) NHL but not in other subtypes of indolent NHL, further corroborating the hypothesis of a superantigen stimulation in this specific histological entity .…”

mentioning

confidence: 77%

Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

Fozza

Corda

Virdis

et al. 2014

European J of Haematology

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Although a number of studies suggest that different immune pathways may play a role in the pathogenesis of non-Hodgkin's lymphomas (NHL), the shape of the T-cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T-cell receptor (TCR) repertoire and the distribution of different T-cell subsets - including regulatory T cells (Treg) - in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T-cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T-cell branch of the immune system of patients with B-cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.

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mentioning

confidence: 77%

Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

Fozza

Corda

Virdis

et al. 2014

European J of Haematology

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“…Prompted by the observations of reduced T-cell counts 24 and the failure of most patients with untreated indolent B-cell lymphomas to respond to hepatitis B vaccination, 27 we present here the results of an unbiased, prospective study to identify and characterize numerical and functional defects in circulating lymphocytes from patients with untreated chronic B-cell malignancies. We used calibrated methodologies for accurate measurements of absolute cell counts rather than relative frequencies as in most published studies.…”

Section: Discussionmentioning

confidence: 99%

“…24 This observation was mostly attributable to a reduction of naive (CD4 ϩ CD45RA ϩ CD27 ϩ ) T helper cells to 51% in FL and 25% in eMZL compared with age-matched controls. No significant changes were noted for central (CD4 ϩ CD45RA Ϫ CD27 ϩ ) and peripheral (CD4 ϩ CD45RA Ϫ CD27 Ϫ ) T helper memory cells (data not shown).…”

Section: Circulating T-cell Subpopulations In Patients With Chronic Bmentioning

confidence: 99%

“…The study population encompassed all persons previously investigated for perturbations of their T-cell receptor (TCR) repertoire. 24 The study was approved by the University of Freiburg institutional ethics committee. All samples were processed for immunophenotyping and in vitro stimulation assays within 2 hours after collection without cryopreservation of cells.…”

Section: Patients and Samplesmentioning

confidence: 99%

“…23 We have previously described a significant reduction in peripheral T helper cells in patients with untreated FL and eMZL. 24 To delineate these observations with respect to CD4 ϩ subpopulations, to explore their functional consequences, and to possibly identify underlying mechanisms, we performed a prospective global characterization of the cellular immune system in untreated patients with indolent B-cell lymphoma compared with age-matched healthy controls.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Definition and characterization of the systemic T-cell dysregulation in untreated indolent B-cell lymphoma and very early CLL

Christopoulos

Pfeifer

Bartholomé

et al. 2011

Blood

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Low absolute CD4+ T cell counts in peripheral blood are associated with inferior survival in follicular lymphoma

Liang

et al. 2016

Tumor Biol.

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Host immunity and tumor microenvironment significantly influence follicular lymphoma (FL) outcomes. Lymphopenia has been identified as a negative prognostic factor for FL. However, there is limited data regarding prognostic value of peripheral blood T lymphocyte subsets, especially absolute CD4 T cell counts (ACD4C) in FL. We studied 127 consecutive FL patients to investigate whether peripheral blood ACD4C or absolute monocytes (AMC) at diagnosis had an impact on FL prognosis. In our cohort, both low ACD4C and high AMC were the parameters associated with inferior progression-free survival (PFS) (P = 0.021 and P = 0.013, respectively) and inferior overall survival (OS) (P = 0.020 and P = 0.005, respectively) by univariate analysis. Multivariate analysis revealed that only low ACD4C was statistically significant in worse PFS (hazard ratio, 2.811; 95 % confidence interval, 1.137-6.950; P = 0.025) and shorter OS (hazard ratio, 3.393; 95 % confidence interval, 1.037-11.105; P = 0.043) independent of FLIPI-2. Evaluation of blood ACD4C could be a useful indicator of outcome in previously untreated FL patients.

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The peripheral helper T-cell repertoire in untreated indolent B-cell lymphomas: evidence for antigen-driven lymphomagenesis

Cited by 11 publications

References 9 publications

Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

Definition and characterization of the systemic T-cell dysregulation in untreated indolent B-cell lymphoma and very early CLL

Low absolute CD4+ T cell counts in peripheral blood are associated with inferior survival in follicular lymphoma

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