Constitutive expression of pore-forming protein in peripheral blood gamma/delta T cells: implication for their cytotoxic role in vivo.

Nakata, M.; Smyth, Mark J.; Norihisa, Y; Kawasaki, Akemi; Shinkai, Yoichi; Okumura, Ko; Yagita, Hideo

doi:10.1084/jem.172.6.1877

Cited by 98 publications

(45 citation statements)

References 16 publications

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“…In this study, we first investigated PFP + cells and their phenotypes in circulating PBL by double staining, using both a rat anti-PFP monoclonal antibody which cross-reacts to human PFP (Nakata et al, 1990) (Rabinowich et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Perforin expression in lymphocytes infiltrated to human colorectal cancer

Nakanishi

Monden²,

Morimoto³

et al. 1991

Br J Cancer

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al., 1985;Young et al., 1986a). PFP released from killer cells forms pores on the target cell membrane and induces cell lysis (Henkart, 1985;Zalman et al., 1986;Young et al., 1986b). Recent success in the cloning of PFP cDNA (Shinkai et al., 1988a;Lichtenheld et al., 1988;Lichtenheld & Podack, 1989;Lowrey et al., 1989) has allowed the examination of mRNA expression of PFP in killer cells. In the T cell lines, PFP gene expression was ascertained in the cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, but not in helper T (Th) cells (Shinkai et al., 1988a;Lichtenheld et al., 1988).The role of tumour infiltrating lymphocytes (TIL) in the defense mechanism of a tumour-bearing host has been thoroughly reported (Werkmeister et al., 1979). It is known that CTL and NK cells directly kill tumour cells (Reinherz et al., 1979;Lanier et al., 1983;Lanier et al., 1986 (v/v) hydrogen peroxidase, freshly prepared ABC complex (Vectastain R ABC Kit, Vector) was applied and followed by incubation for 30 min. After the excess complex was washed out, the localisation of PFP was visualised by incubating the sections for 5 min in freshly prepared Tris-HCI containing both 0.02% (w/v) 3.3'-diaminobenzidine tetrahydrochloride (Sigma, St Louis, MO) and 0.03% (v/v) hydrogen peroxide. The nuclei were counterstained with haematoxylin.

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Section: Discussionmentioning

confidence: 99%

Perforin expression in lymphocytes infiltrated to human colorectal cancer

Nakanishi

Monden²,

Morimoto³

et al. 1991

Br J Cancer

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“…Expressed by natural killer (NK) cells, ␥␦ ϩ T cells, CD8 ϩ cytotoxic T lymphocytes (CTLs), and some other T-cell subsets (9)(10)(11), pfp is essential for delivery of proapoptotic granzymes, which initiate the destruction of virus-infected or transformed cells (12)(13)(14). We have previously demonstrated that approximately half of a cohort of aging pfp-deficient mice developed spontaneous mature B-cell lymphomas between 300 and 750 days from birth (15)(16)(17).…”

mentioning

confidence: 99%

Perforin-mediated suppression of B-cell lymphoma

Bolitho

Street

Westwood

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Pore-forming proteins are constitutively expressed by peripheral blood cdT cells, 34 suggesting that these proteins play a vital role in cdT-cell cytotoxicity. Moreover, Vc9d2T lymphocytes were reported to kill microorganisms residing in intracellular compartments in a perforin and granzyme-dependant manner.…”

Section: Discussionmentioning

confidence: 99%

CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity

Zhao

Cui

et al. 2011

Cell Mol Immunol

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Adoptive cell-transfer therapy (ACT) has been reported to suppress growing tumors and to overcome tumor escape in animal models. As a candidate ACT effector, c9d2T cells can be activated and expanded in vitro and in vivo and display strong antitumor activity against colorectal, lung, prostate, ovarian and renal cell carcinomas. However, it is difficult to obtain a large enough number of cdT cells to meet the need for immunotherapy that can overcome the cancer patients' immune suppressive tumor microenvironment. In previous studies, our lab confirmed that c9d2T cells recognized tumor cells via the CDR3d region of the cd-T-cell receptor (TCR). We constructed full-length human peripheral blood mononuclear cell (PBMC)-derived c9 and d2 chains in which the CDR3 region was replaced by an ovarian epithelial carcinoma (OEC)-derived CDR3. We transferred the CDR3d-grafted c9d2TCR into peripheral blood lymphocytes (PBLs) to develop genetically modified c9d2T cells. In vitro studies have shown that these CDR3d-grafted c9d2T cells can produce cytokines after stimulation with tumor cell extracts and exhibit cytotoxicity towards tumor cells, including human OEC and cervical adenocarcinoma. CDR3d-grafted c9d2T cells adoptively transferred into nude mice bearing a human OEC cell line demonstrated significant antitumor effects. These results indicate that CDR3d-grafted c9d2T cells might be candidates for clinical tumor immunotherapy.

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Constitutive expression of pore-forming protein in peripheral blood gamma/delta T cells: implication for their cytotoxic role in vivo.

Cited by 98 publications

References 16 publications

Perforin expression in lymphocytes infiltrated to human colorectal cancer

Perforin expression in lymphocytes infiltrated to human colorectal cancer

Perforin-mediated suppression of B-cell lymphoma

CDR3δ -grafted γ9δ2T cells mediate effective antitumor reactivity

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