T cell receptor V gene usage by CD4<sup>+</sup> and CD8<sup>+</sup> peripheral blood T lymphocytes in immune thrombocytopenic purpura

Hedlund-Treutiger, Iris; Elinder, Göran; Wigzell, Hans; Grünewald, Johan; Wahlström, Jan

doi:10.1111/j.1651-2227.2004.tb02988.x

Cited by 6 publications

(7 citation statements)

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“…The TCR repertoire has been frequently studied in various diseases, but mainly in blood samples (6,14,15,19,(21)(22)(23)37,39), and more rarely in injured organs (3)(4)(5)(6)(7)(8)(9)(10)17,20,21,24,(32)(33)(34). However, it is well known that circulating lymphocytes do not exactly reflect the situation in tissues where pathologic lesions occur (6,17,23,33,37).…”

Section: Discussionmentioning

confidence: 99%

“…Such an approach by flow cytometry proved to be efficient in detecting skewing of the TCR-repertoire in blood samples. Indeed, oligoclonal expansions or restrictions of some families have been demonstrated in allergy (14), autoimmune disease (15)(16)(17)(18)(19), infection (20)(21)(22)(23), cancer (24,25), and immunodeficiency (26,27). In addition, homogeneous expansions have been characterized in T-cell lymphoproliferative disorders (11,(28)(29)(30)(31).…”

Section: (Cdr3)mentioning

confidence: 99%

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Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

et al. 2009

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Analysis of the T-cell receptor (TCR) repertoire by flow cytometry proved to be relevant for investigating T-cell diversity and detecting reactive cells in blood samples. We used this approach to characterize non-malignant T-lymphocytes in lymph nodes and give insights into their origin. The TCR repertoire of CD41 and CD81 T-cells from 81 lymph nodes was analyzed with a four-color flow cytometer using a wide panel of 25 anti-Vb monoclonal antibodies. Flow cytometry proved to be a useful and informative technique. We demonstrated a diversified TCR-Vb repertoire, and only low level expansions, in 53% of the samples. They involved nearly all Vb families, were more frequent in the CD81 subset of older patients, but were not related to pathology. No evidence could be demonstrated in favor of stimulation by common antigens. Interestingly, the TCR-Vb repertoire proved to be very similar in lymph nodes and blood samples. Our results argue that in the cases studied, lymph node enlargement is mainly due to an increased homing of circulating T-cells. They also provide reference values for expression of 25 TCR-Vb in lymph nodes, which could serve as a basis for further applications in diagnosis of T-cell lymphoproliferative disorders. ' 2009 International Society for Advancement of Cytometry

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Section: Discussionmentioning

confidence: 99%

Section: (Cdr3)mentioning

confidence: 99%

Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

et al. 2009

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“…However, these mechanisms cannot account for all observations made in ITP. It has become evident that T‐lymphocytes abnormalities might have pathogenetic importance in ITP (Hedlund‐Treutiger et al , 2004; Panitsas et al , 2004). Most recently, in vitro studies suggested that cytotoxic T‐lymphocytes (CTL) (CD8 + ) might be involved in the pathogenesis of chronic ITP through the cell‐mediated destruction of autologous platelets (Olsson et al , 2003; Zhang et al , 2006).…”

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confidence: 99%

CD8⁺ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura

Wang²,

Zhao

et al. 2007

Br J Haematol

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Summary To investigate the effect and mechanism of the CD8+ T cells in bone marrow on autologous megakaryocytopoiesis in idiopathic thrombocytopenic purpura (ITP) patients, we prepared bone marrow mononuclear cells (MNCs) from 15 chronic ITP patients and 13 controls. MNCs were cultured in vitro directly (MNC group) or after depleting CD8+ T cells (CD8+ T‐dep group) or adding purified autologous CD8+ T cells to CD8+ T‐dep MNCs (Coculture group) or adding dexamethasone to the coculture (DEX group) all in semi‐solid and liquid culture systems. The quantity and quality of megakaryocytes were measured. The megakaryocyte count was increased in the presence of autologous CD8+ T cells of patients with chronic ITP, while platelet production was reduced. In addition, lower percentages of polyploidy and apoptotic megakaryocytes, and higher levels of soluble Fas (sFas) in supernatant were observed. Dexamethasone successfully corrected this effect of CD8+ T cells on autologous megakaryocytopoiesis. These studies provide evidence that activated CD8+ T cells in bone marrow of patients with chronic ITP might suppress megakaryocyte apoptosis, leading to impaired platelet production. Megakaryocyte apoptosis would be a novel target for the management of ITP.

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“…, 2005; Kato et al. , 2000; Hedlund‐Treutiger et al. , 2004; Hedlund‐Treutiger, Wahlstrom & Elinder, 1998; Li et al ., 2005).…”

Section: Discussionunclassified

“…, 2005). Skewing expression and clonal expansion of TCR Vβ repertoire with frequent use of Vβ3, 6, 10, 13 and 14 were also observed in ITP (Hedlund‐Treutiger, Wahlstrom & Elinder, 1998; Hedlund‐Treutiger et al. , 2004), and the abnormalities were reverted in responders after treatment with rituximab (Stasi et al.…”

Section: Introductionmentioning

confidence: 99%

The feature of clonal expansion of TCR Vβ repertoire, thymic recent output function and TCRζ chain expression in patients with immune thrombocytopenic purpura

Zhang

Chen

et al. 2009

Int J Lab Hematology

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In order to identify the feature of T cells immune status in idiopathic/immune thrombocytopenic purpura (ITP) patients, TCR Vbeta repertoire, T-cell receptor (TCR) excision DNA circles (TRECs) and TCRzeta chain gene expression were examined. Reverse-transcriptase polymerase chain reaction, genescan and real-time PCR techniques were used to analyze. DNA and cDNA from peripheral blood mononuclear cells (PBMCs) of 18 ITP patients were investigated and 25 normal individuals served as control. The results showed that only 4-11 Vbeta subfamilies could be detected in each ITP case. The most frequently expressed Vbeta subfamilies were Vbeta2 and Vbeta3, while 11 Vbeta subfamilies were absent. Clonal expansion of Vbeta T cells were found in all patients. The most frequent clonal expansion T cell was Vbeta21. The number of TRECs in ITP patients (2.60 +/- 2.99 copies/1000 PBMCs) was not significant different, compared with control (3.76 +/- 3.42 copies/1000 PBMCs). The expression level of TCRzeta gene was significantly lower in ITP samples than those in control (P = 0.017). In summary, T cells in ITP patients were characterized by restricted expression of TCR Vbeta subfamilies and clonal expansion predominant in Vbeta21. The alteration of peripheral TCR Vbeta repertoire pattern may not relate to the thymic, recent output function in ITP patients. Our report is the first description of decreased TCRzeta mRNA level in the majority of ITP patients.

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T cell receptor V gene usage by CD4⁺ and CD8⁺ peripheral blood T lymphocytes in immune thrombocytopenic purpura

Abstract: Overall T cell expansion frequency was the same as in healthy individuals. However, the presence of expansions that normalized with treatment suggests the presence of specific T cells implicated in the pathogenesis of ITP.

Cited by 6 publications

References 29 publications

Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

CD8⁺ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura

The feature of clonal expansion of TCR Vβ repertoire, thymic recent output function and TCRζ chain expression in patients with immune thrombocytopenic purpura

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T cell receptor V gene usage by CD4+ and CD8+ peripheral blood T lymphocytes in immune thrombocytopenic purpura

Abstract: Overall T cell expansion frequency was the same as in healthy individuals. However, the presence of expansions that normalized with treatment suggests the presence of specific T cells implicated in the pathogenesis of ITP.

Cited by 6 publications

References 29 publications

Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

Efficient characterization of the TCR repertoire in lymph nodes by flow cytometry

CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura

The feature of clonal expansion of TCR Vβ repertoire, thymic recent output function and TCRζ chain expression in patients with immune thrombocytopenic purpura

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T cell receptor V gene usage by CD4⁺ and CD8⁺ peripheral blood T lymphocytes in immune thrombocytopenic purpura

CD8⁺ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura