Characterization of the γδ T cell response to acute leukemia

Meeh, Paul F.; King, Michelle; O’Brien, Rebecca L.; Muga, Stephanie J.; Buckhalts, Philip; Neuberg, Ronnie W.; Lamb, Lawrence S.

doi:10.1007/s00262-005-0094-6

Cited by 47 publications

(39 citation statements)

References 34 publications

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“…Shen et al (16) also showed similar results and they postulated that the presence of TCR Vd clonality in a few T cells is a normal phenomenon and a result of non-specific random proliferation. A previous work showed TCR Vd 1 was preferably expressed in the hu man intestinal epithelial cells, and its expression was also frequently found in autoimmune diseases, tu mors and bronchial asthma (18). Our results re vealed the TCR Vd 6 T cells had an increased trend toward oligoclonal proliferation following SIT.…”

Section: Discussionsupporting

confidence: 73%

Effects of Immunotherapy on the Distribution and Clonality of TCR Vγ and Vδ Subfamily T Cells in Allergic Rhinitis Patients

Yang¹,

Li²,

Wu³

et al. 2012

Journal of Medical Biochemistry

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Summary: The aim of this study was to investigate the changes in the peripheral specific IgE level, distribution of TCR Vg and Vd subfamily T cells and mRNA expressions of TCR Vg I-III following specific immunotherapy (SIT) with house-dust-mite extract in allergic rhinitis (AR) patients. Ten AR patients undergoing SIT with house-dust-mite extract for 1 year were recruited. Quanti tative analysis of immunofluorescence was performed to detect the serum specific IgE (sIgE) level before and after SIT; RT-PCR-genescan analysis was employed to detect the mRNA expressions of TCR Vg (I-III) and Vd (1-8) in the peripheral mononuclear cells followed by analysis of T cell clonality. Real-time quantitative PCR was applied to detect the expressions of TCR Vg I-III genes. Ten healthy volunteers served as controls. For AR patients, SIT treatment could improve the symptoms, but the serum sIgE level was not markedly decreased. Before SIT, the expressions of TCR Vg I-III gene were similar between AR patients and controls (P>0.05) but markedly decreased after SIT in AR patients (P<0.05 in TCR VgI and VgII). The expressions of TCR Vd (1-8) before and after SIT were 5.3±0.82 and 4.9±0.57, respectively, and that in healthy controls was 5.2±1.40. Vd1, 2, 3 and 6 were the most common genes found in these patients. Significant difference in the TCR Vd6 subfamily T cells was found between the two groups. Polyclonal or biclonal proliferation was found in the T cells of patients before SIT and in healthy controls, but oligoclonal proliferation in only 1 subject before SIT. After SIT, the proportion of patients with oligoclonal proliferation of T cells (6/10) was markedly increased (P<0.05). SIT for 1 year could alter the expressions of TCR Vg I-III genes, the Kratak sadr`aj: Cilj ove studije bio je da se istra`e promene u nivou specifi~nog IgE u perifernoj krvi, distribuciji T }elija iz potporodice TCR Vg i Vd i ekspresiji TCR Vg I-III u mRNK posle specifi~ne imunoterapije (SIT) sa ekstraktom grinja iz ku}ne pra{ine kod pacijenata sa alergijskim rinitisom (AR). Uklju~eno je 10 pacijenata sa AR le~enih specifi~nom imunoterapijom sa ekstraktom grinja iz ku}ne pra{ine tokom 1 godine. Obavljena je kvantitativna analiza imunofluorescencijom kako bi se odredio nivo specifi~nog IgE (sIgE) u serumu pre i posle SIT; primenjena je RT-PCRgenescan analiza radi odre|ivanja ekspresije TCR Vg (I-III) i Vd (1-8) u mRNK u perifernim mononuklearnim }elijama posle ~ega je obavljena analiza klonalnosti T }elija. Kvantitativna PCR analiza u realnom vremenu sprovedena je kako bi se odredila ekspresija TCR Vg I-III gena. Deset zdravih dobrovoljaca slu`ilo je kao kontrolna grupa. Kod pacijenata sa AR, tretman SIT olak{ao je simptome, ali nivo sIgE u serumu nije se zna~ajno snizio. Pre SIT, ekspresija TCR Vg I-III gena bila je sli~na kod pacijenata sa AR i kontrolnih subjekata (P>0,05), ali se zna~ajno snizila posle SIT kod pacijenata sa AR (P>0,05 u TCR VgI i VgII). Ekspresija TCR Vd (1-8) pre i posle SIT bila je 5,3±0,82 i 4,9±0,57, a kod zdravih subjekata 5,2±1...

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Section: Discussionsupporting

confidence: 73%

Effects of Immunotherapy on the Distribution and Clonality of TCR Vγ and Vδ Subfamily T Cells in Allergic Rhinitis Patients

Yang¹,

Li²,

Wu³

et al. 2012

Journal of Medical Biochemistry

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“…Although the biological implications of this finding are incompletely understood, previous studies suggest both a depletion of the Vd2 subset and activation and expansion of the Vd1 subset may be responsible for this. [49][50][51][52][53][54][55][56][57] Whether these findings are unique to T cell-depleted grafts is not clear because there are very few publications on immune reconstitution post HSCT that report on recovery of the gd T cell subpopulation. In general, studies on immune reconstitution post HSCT demonstrate no significant qualitative differences between recipients of T cell-depleted and recipients of unmodified grafts, although immune reconstitution is relatively delayed in the T celldepleted group.…”

Section: Discussionmentioning

confidence: 99%

Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation

Godder

Henslee‐Downey

Mehta

et al. 2007

Bone Marrow Transplant

260

247

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Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival (LFS) in many but not all patients with acute leukemia. This is an eight-year followup to our previous study showing a survival advantage to patients with an increased cd T cells following ASCT. cd T cell levels were collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n ¼ 77; acute myelogenous leukemia (AML) n ¼ 76) undergoing partially mismatched related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity of three antigens was 37% in the graft-versushost disease (GvHD) and 29% in the rejection directions. All patients received a partially T cell-depleted graft using T10B9 (n ¼ 46) or OKT3 (n ¼ 107). Five years LFS and overall survival (OS) of patients with increased cd compared to those with normal/decreased numbers were 54.4 vs 19.1%; Po0.0003, and 70.8 vs 19.6% Po0.0001, respectively, with no difference in GvHD (P ¼ 0.96). In a Cox multivariate analysis, normal/decreased cd (hazard ratio (HR) 4.26, P ¼ 0.0002) and sex mismatch (HR 1.45 P ¼ 0.049) were associated with inferior LFS. In conclusion, cd T cells may facilitate a graft-versus-leukemia (GvL) effect, without causing GvHD. Further evaluations of this effect may lead to specific immunotherapy for patients with refractory leukemia.

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“…5,6 The anti-leukemic role of gd T cells was suggested by a correlation between Vd1 T cells expansion and prognosis following AHSCT. 7,8 Aside from Vd1 T cells, Vg9Vd2 T cells, the main circulating subset, account for 1-10% of human T lymphocytes. Their T cell receptors (TCR) sense non-peptidic-phosphorylated phosphoAntigens (pAgs), such as isopentenyl diphosphate (IPP), an intermediary metabolite of the human mevalonate pathway.…”

Section: Introductionmentioning

confidence: 99%

BTN3A molecules considerably improve Vγ9Vδ2T cells-based immunotherapy in acute myeloid leukemia

et al. 2016

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Given their recognized ability to kill acute myeloid leukemia (AML) blasts both in vitro and in vivo, Vg9Vd2 T cells are of growing interest in the design of new strategies of immunotherapy. We show that the Butyrophilin3A (BTN3A, CD277) subfamily is a critical determinant of Vg9Vd2 TCR-mediated recognition of human primary AML blasts ex vivo. Moreover, anti-BTN3A 20.1 agonist monoclonal antibodies (mAbs) can trigger BTN3A on AML blasts leading to further enhanced Vg9Vd2 T cell-mediated killing, but this mAb had no enhancing effect upon NK cell-mediated killing. We show that monocytic differentiation of primary AML blasts accounts for their AminoBisphosphonate (N-BP)-mediated sensitization to Vg9Vd2 T cells. In addition, anti-BTN3A 20.1 mAbs could specifically sensitize resistant blasts to Vg9Vd2 T cells lysis and overcome the poor effect of N-BP treatment on those blasts. We confirmed the enhancement of Vg9Vd2 T cells activity by anti-BTN3A 20.1 mAb using a human AML xenotransplantation mouse model. We showed that anti-BTN3A 20.1 mAb combined with Vg9Vd2 T cells immunotherapy could increase animal survival and decrease the leukemic burden in blood and bone marrow. These findings could be of great interest in the design of new immunotherapeutic strategies for treating AML.

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Characterization of the γδ T cell response to acute leukemia

Cited by 47 publications

References 34 publications

Effects of Immunotherapy on the Distribution and Clonality of TCR Vγ and Vδ Subfamily T Cells in Allergic Rhinitis Patients

Effects of Immunotherapy on the Distribution and Clonality of TCR Vγ and Vδ Subfamily T Cells in Allergic Rhinitis Patients

Long term disease-free survival in acute leukemia patients recovering with increased γδ T cells after partially mismatched related donor bone marrow transplantation

BTN3A molecules considerably improve Vγ9Vδ2T cells-based immunotherapy in acute myeloid leukemia

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