Skewed T cell receptor repertoire of Vδ1+ γδ T lymphocytes after human allogeneic haematopoietic stem cell transplantation and the potential role for Epstein–Barr virus-infected B cells in clonal restriction

Fujishima, Naohito; Hirokawa, Makoto; Fujishima, Masumi; Yamashita, Junsuke; Saitoh, H; Ichikawa, Yoshikazu; Horiuchi, Takahiro; Kawabata, Yoshinari; Sawada, Kenichi

doi:10.1111/j.1365-2249.2007.03388.x

Cited by 69 publications

(51 citation statements)

References 34 publications

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“…Among patients who have had allogenic stem cell transplantation, these T cells are of donor origin and are likely to be induced by EBV-infected B cells. 27 On the other hand, in patients of solid organ transplants like renal transplants, the T cells are of patient/ recipient origin and represent allo-reactive T cells against the transplanted organ. The presence of expanded T-cell clones in the peripheral blood has been shown to have a negative impact on the long-term graft function (survival of the transplanted kidney).…”

Section: Discussionmentioning

confidence: 99%

Presence of monoclonal T-cell populations in B-cell post-transplant lymphoproliferative disorders

et al. 2011

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As has been previously shown, the lack of immune surveillance plays a major role in the unchecked proliferation of Epstein-Barr virus (EBV)-infected B cells in the pathogenesis of B-cell post-transplant lymphoproliferative disorders. We hypothesised that the lack of immune surveillance should possibly also affect T cells, and this should lead to subsequent emergence of T-cell clones. The presence of both B-and T-cell clones in post-transplant lymphoproliferative disorders samples has rarely been demonstrated in the past. We systematically evaluated 26 B-cell post-transplant lymphoproliferative disorder, 23 human immune deficiency virus-associated B-cell lymphoma and 10 immune-competent diffuse large B-cell lymphoma samples for B-and T-cell clonality (polymerase chain reaction and heteroduplex analysis using BIOMED-2 protocol), T-cell subsets (immunohistochemistry) and EBV association (in situ hybridisation using EBER). One-half of B-cell posttransplant lymphoproliferative disorders showed evidence of monoclonal T-cell expansion, and among the T cells present in the tissue samples, CD8-positive cells predominated. Although 9/13 (69%) B-cell posttransplant lymphoproliferative disorders with the presence of monoclonal T-cell population had a CD4:CD8 ratio of r0.4, 0/13 of the cases without monoclonal T-cell expansion had a ratio r0.4 (P ¼ 0.002). Only 2/26 (8%) demonstrated significant cytological atypia in the CD3/CD8-positive cells. There was no association between EBV and presence of T-cell clones. T-cell clones were not identified in lymphomas other than B-cell post-transplant lymphoproliferative disorders. Among 53.8% cases of EBV-positive B-cell post-transplant lymphoproliferative disorders with associated clonal expansion of T-cells tested, none had EBV-positive T cells. We conclude that half of B-cell post-transplant lymphoproliferative disorders are associated with clonal expansion of CD8-positive T cells, most of which do not amount to the coexistence of a T-cell post-transplant lymphoproliferative disorders.

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Section: Discussionmentioning

confidence: 99%

Presence of monoclonal T-cell populations in B-cell post-transplant lymphoproliferative disorders

et al. 2011

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“…For instance, human V␥9V␦2 T cells can kill herpes simplex virus (HSV)-, Epstein-Barr virus (EBV)-, or CMV-infected target cells in an HLA-unrestricted manner in vitro (7,13,17). IPP-activated V␥9V␦2 T cells not only kill human immunodeficiency virus (HIV)-infected target cells but also inhibit viral replication by releasing certain CCR5 ligand chemokines to block the HIV entry coreceptor CCR5 (30,31).…”

Section: Discussionmentioning

confidence: 99%

Type 1 Responses of Human Vγ9Vδ2 T Cells to Influenza A Viruses

Qin

Liu

Zheng

et al. 2011

J Virol

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␥␦ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human V␥9V␦2 T cells participated in antiinfluenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of ␥␦ T cells to influenza virus. In this study, we found that V␥9V␦2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-␥). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated ␥␦ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-␥ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in V␥9V␦2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of V␥9V␦2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human V␥9V␦2 T cells against influenza virus infection.

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“…cDNA was then used to amplify the Vd1 TCR chain complementary determining region 3 (CDR3) employing primers specific for either the variable Vd1-region (designated VD1) or the constant Cd-region (CD1) as described by Fujishima et al [10]. Polymerase chain reaction (PCR) was performed for 40 cycles in a 25 ll reaction mixture containing 0.2 mm of each primer and 1 unit of Taq polymerase (Platinum Taq, Invitrogen) using the following PCR-conditions: denaturation at 94°C for 1 min; annealing at 55°C for 1 min; extension at 72°C for 1.5 min.…”

Section: Sequencing Of the Vd1 Tcr Chain Complementary Determining Rementioning

confidence: 99%

“…Vd1 T cells recognize heterogeneous and not well-defined antigens, which in most instances appear to be self-antigens whose expression is induced by cell stress, bacterial and particularly viral infections [26]. Expansion of peripheral blood cd T cells and/or skewed TCR repertoires of Vd1 T cells have indeed been observed in patients with various viral infections [10,[27][28][29][30]. For instance, Vd1 cells substantially expand in the course of HIV [31,32] and CMV [27] infections.…”

Section: Vd1 T Cells [%(Sem)] Vd2 T Cells [%(Sem)]mentioning

confidence: 99%