Antilymphoma activity of human gamma delta T-cells in mice with severe combined immune deficiency
| Autor: | V, Malkovska, F K, Cigel, N, Armstrong, B E, Storer, R, Hong |
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| Rok vydání: | 1992 |
| Předmět: |
Receptors
Antigen T-Cell gamma-delta Mice SCID Lymphocyte Activation Burkitt Lymphoma Immunotherapy Adoptive Growth Inhibitors Lymphocyte Depletion Clone Cells Killer Cells Natural Mice Injections Intravenous Leukocytes Mononuclear Animals Humans Severe Combined Immunodeficiency Injections Intraperitoneal T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer research. 52(20) |
| ISSN: | 0008-5472 |
| Popis: | Human Burkitt lymphoma (Daudi) cells grow as disseminated tumors in mice with severe combined immune deficiency (SCID) after either i.v. or i.p. injection. These cells are lysed in vitro by human V gamma 9/V delta 2 T-cells that recognize the groEL homologue on the Daudi cell surface. We report that both Daudi cell-stimulated peripheral blood mononuclear cells (Daudi-PBMC) containing 41-95% of V gamma 9/V delta 2 T-cells and V gamma 9/V delta 2 T-cell clones prolong the survival of SCID mice given inoculations of a lethal dose of Daudi cells. Groups of 6-8-week-old SCID mice were given inoculations i.v. or i.p. of 10(5) Daudi cells followed (through different injection sites) by: (a) 10(7) Daudi-PBMC; or (b) 10(7) unstimulated PBMC; or (c) 0.9% saline solution. All animals in groups (b) and (c) died of disseminated lymphoma, and their survival was significantly shorter than that of mice in group (a) (P0.001 for both i.v. and i.p. routes). Significant antitumor effects were also detected when Daudi-PBMC were injected 4 days before or 4 days after Daudi cells (P0.05). In vivo depletion of murine natural killer cells by anti-asialo GM-1 rabbit antiserum did not affect survival, suggesting that these cells did not contribute to lymphoma killing. Daudi-PBMC did not exert in vivo antitumor activity against the control Raji lymphoma. Mice receiving i.p. injections of Daudi cells followed by cytotoxic V gamma 9/V delta 2 T-cell clones also survived significantly longer (P0.05 for 3 different clones) than animals given Daudi cells alone or Daudi cells followed by noncytotoxic gamma delta T-cell clones. Our results indicate that this model system can be used for studies of human antilymphoma T-cell responses in vivo. |
| Databáze: | OpenAIRE |
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