Comparison of Cytolytic and Proliferative Activities of Human γδ and αβ T Cells From Peripheral Blood Against Various Human Tumor Cell Lines

Ensslin, Angela; Formby, Bent

doi:10.1093/jnci/83.21.1564

Cited by 46 publications

(26 citation statements)

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“…These results are in agreement with the reports of Fisch et al (1990) and Ciccone et al (1988), who demonstrated that TCR ␥␦ MAb inhibited cytotoxicity against Daudi cells. In contrast, Zocchi et al (1990) and Ensslin and Formby (1991) reported that the killing of ovarian or lung tumor cells appeared to be independent of the ␥␦ TCR, though activation via the ␥␦ TCR regulates the killing potential of these cells. These investigators attributed these differences to the concentrations of MAb used as conformational changes or downregulation of the ␥␦ TCR may have occurred.…”

Section: Discussionmentioning

confidence: 95%

Human gamma delta T cells recognize heat shock protein‐60 on oral tumor cells

Laad¹,

Thomas²,

Fakih³

et al. 1999

Int. J. Cancer

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In the hemato-lymphoid system, a vast majority of T cells (Ͼ90%) express antigen receptors composed of clonally variable alpha beta (␣␤) heterodimers in association with the invariant components of the CD3 complex, while a small population of T cells (Ͻ10%) express the gamma delta (␥␦) T-cell receptor (TCR) (Kabelitz, 1992).Among the known ligands for ␥␦ T cells, heat shock proteins (hsps) and phospholigands have gained particular importance because of their wide distribution and oligoclonal stimulation of ␥␦ T cells (Kaufmann, 1996). The hsps are ubiquitous and highly conserved proteins expressed at elevated levels under stress (Kaufmann, 1990). It has been suggested that the focus of ␥␦ T cells on hsps would promote a rapid response to cell stress caused by a variety of insults, including infection, inflammation and neoplastic transformation. Evidence for the role of hsp molecules in tumor cell recognition by ␥␦ T cells has been accumulating. Over-expression of hsp27 achieved by transfection in the breast carcinoma-derived cell line MCF-7 made it susceptible to ␥␦ T-cell killing, whereas cytotoxicity mediated by NK or LAK cells was not increased (Mahvi et al., 1993). The Burkitt's lymphoma cell line Daudi is known to selectively activate V␥9/V␦2 T cells. It was further demonstrated that the reactivity of ␥␦ T cells toward Daudi tumor cells could be inhibited by anti-hsp60 antibodies Fisch et al., 1990;Kaur et al., 1993). In lung carcinomas, where large numbers of ␥␦ T cells have been localized, overexpression of hsp72 was observed (Ferrarini et al., 1994).The present investigations were focused on understanding the potential involvement of the peripheral blood ␥␦ T cells in immune responses to oral squamous cell carcinoma. The ␥␦ T cells were expanded from the peripheral blood of oral cancer patients by co-culturing peripheral blood lymphocytes (PBLs) with Daudi Burkitt's lymphoma cells. The expanded cell population contained a major population of ␥␦ T cells expressing the V␥9 and V␦2 receptors. These ␥␦ T cells exhibited increased cytotoxicity against Daudi and oral tumor cells compared with other tumor targets. Monoclonal antibodies (MAbs) to hsp60 inhibited the cytotoxicity of ␥␦ T cells against both tumor targets, suggesting that hsp60 molecules expressed on the oral tumor cells serve as possible ligands for the ␥␦ T cells. MATERIAL AND METHODS PatientsBlood samples were collected from oral cancer patients (n ϭ 10) with clinically and histologically proven squamous cell carcinoma staged according to the TNM system of UICC (3rd ed.). Tumor biopsies were obtained from a separate set of oral cancer patients undergoing surgery. None of the patients had received chemotherapy, radiotherapy or immunotherapy before surgery. MAbsThe following antibodies were used. TCR␦1 (anti-TCR␥␦), BMA 031(anti-TCR␣␤), Ti␥A (anti-V␥9), BB3 (anti-V␦2) and 23D12 (anti-V␥2/3/4) were obtained as gifts from Dr. D. Kabelitz (Langen, Germany) and Dr. R.L.H. Bolhuis (Rotterdam, The Netherlands and 4A11 (anti V␥4) was obtained as a gift f...

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Section: Discussionmentioning

confidence: 95%

Human gamma delta T cells recognize heat shock protein‐60 on oral tumor cells

Laad¹,

Thomas²,

Fakih³

et al. 1999

Int. J. Cancer

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“…There are several candidate antigens expressed on various neoplastic cells that would support ␥␦ + T cell-based cytotoxicity outside the recognition of MHC-associated peptides. Esslin and Formby 7 showed that in vitro activated peripheral blood ␥␦ + T cells possess MHC non-restricted cytolytic activity towards selected human tumor cell lines when compared to similarly activated ␣␤ + T cells. Others have shown that heat shock proteins, [17][18][19] TCT.1 20 and the nonclassical human MHC antigens MICA and MICB 16 also function as ligands for ␥␦ + T cells.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] Although few studies have addressed the role of donor-derived ␥␦ + T cells in BMT, it is known that ␥␦ + T cells can mediate direct cytolytic activity to some human tumor cell lines. 7,8 We previously reported a series of 10 leukemia patients who developed a persistent increase in donor-derived circulating CD3 + CD4 Ϫ CD8 Ϫ V␦1 + ␥␦ + T cells between 60 and 270 days post BMT. Eight of these patients are surviving and remain free of disease (80%) at 5.5 years following BMT, as compared to 10/33 with a normal number of ␥␦ + T cells (P = 0.009).…”

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confidence: 99%

Human γδ+ T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response

Lamb

Musk

et al. 2001

Bone Marrow Transplant

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Summary:Refractory acute lymphoblastic leukemia (ALL) is often incurable, and relapse rates following allogeneic bone marrow transplantation (BMT) remain high. We have reported that patients who develop increased numbers of ␥␦ + T cells soon after BMT are significantly less likely to relapse. We now show in seven donor/recipient pairs that donor-derived V␦1 + CD4 − CD8 − ␥␦ + T cells are activated and proliferate in response to recipient primary ALL blasts. In addition, these cells have been shown to bind and lyse the recipient ALL blasts. Separately, ␥␦ + T cells proliferate poorly or not at all in mixed lymphocyte culture against HLA-mismatched unrelated stimulator cells. These observations suggest that allogeneic ␥␦ + T cells could be an effective immunotherapeutic strategy against refractory disease without the risk of graft-versus-host disease. Bone Marrow Transplantation (2001) 27, 601-606.

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“…They have the ability to simultaneously recognize and respond to phosphorylated nonpeptide Ags (phosphoantigens [PAgs]) (10), molecules expressed on cells undergoing neoplastic transformation (11) in an HLA-unrestricted fashion (12), and exert specific lysis of tumor cells (13). Vg9Vd2 T cells are thus involved in tumor immune surveillance (14)(15)(16), notably against epithelial cells carcinomas (17-21) and some hematopoi-etic cells malignancies (8,16,22), but their involvement against AML has not been reported so far. Most importantly, because of their unique ability to respond to PAgs, we have known for .10 y how to easily amplify and activate Vg9Vd2 T cells ex vivo with the phosphorylated bromohydrin (BrHPP) analog that mimics the biological properties of natural PAgs (23).…”

Section: In Addition To Conventional Mhc Class I-restricted Cd8mentioning

confidence: 99%

Human Vγ9Vδ2 T Cells Specifically Recognize and Kill Acute Myeloid Leukemic Blasts

Gertner-Dardenne

Castellano

Mamessier

et al. 2012

The Journal of Immunology

114

101

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Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that Vγ9Vδ2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment.

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Comparison of Cytolytic and Proliferative Activities of Human γδ and αβ T Cells From Peripheral Blood Against Various Human Tumor Cell Lines

Cited by 46 publications

References 0 publications

Human gamma delta T cells recognize heat shock protein‐60 on oral tumor cells

Human gamma delta T cells recognize heat shock protein‐60 on oral tumor cells

Human γδ+ T lymphocytes have in vitro graft vs leukemia activity in the absence of an allogeneic response

Human Vγ9Vδ2 T Cells Specifically Recognize and Kill Acute Myeloid Leukemic Blasts

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