DOI: 10.1084/jem.20031981. Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and γδ T Cells

Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and γδ T Cells

10.1084/jem.20031981

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Few studies have demonstrated that innate lymphocytes play a major role in preventing spontaneous tumor formation. We evaluated the development of spontaneous tumors in mice lacking β-2 microglobulin (β2m; and thus MHC class I, CD1d, and CD16) and/or perforin, since these tumor cells would be expected to activate innate effector cells. Approximately half the cohort of perforin gene-targeted mice succumbed to spontaneous disseminated B cell lymphomas and in mice that also lacked β2m, the lymphomas developed earlier (by more than 100 d) and with greater incidence (84%). B cell lymphomas from perforin/β2m gene-targeted mice effectively primed cell-mediated cytotoxicity and perforin, but not IFN-γ, IL-12, or IL-18, was absolutely essential for tumor rejection. Activated NK1.1+ and γδTCR+ T cells were abundant at the tumor site, and transplanted tumors were strongly rejected by either, or both, of these cell types. Blockade of a number of different known costimulatory pathways failed to prevent tumor rejection. These results reflect a critical role for NK cells and γδTCR+ T cells in innate immune surveillance of B cell lymphomas, mediated by as yet undetermined pathway(s) of tumor recognition.

Bibliography

Street, S. E. A., Hayakawa, Y., Zhan, Y., Lew, A. M., MacGregor, D., Jamieson, A. M., Diefenbach, A., Yagita, H., Godfrey, D. I., & Smyth, M. J. (2004). Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and Î³Î´ T Cells. The Journal of Experimental Medicine, 199(6), 879â884.

Authors 10

Shayna E.A. Street (first)
Yoshihiro Hayakawa (additional)
Yifan Zhan (additional)
Andrew M. Lew (additional)
Duncan MacGregor (additional)
Amanda M. Jamieson (additional)
Andreas Diefenbach (additional)
Hideo Yagita (additional)
Dale I. Godfrey (additional)
Mark J. Smyth (additional)

References 34 Referenced 206

10.1002/eji.1830251246 / Eur. J. Immunol. (1995)
10.1084/jem.188.9.1611 / J. Exp. Med. (1998)
10.1084/jem.191.4.661 / J. Exp. Med. (2000)
10.4049/jimmunol.165.5.2665 / J. Immunol. (2000)
10.1084/jem.192.5.755 / J. Exp. Med. (2000)
10.4049/jimmunol.162.11.6658 / J. Immunol. (1999)
10.1182/blood.V97.1.192 / Blood. (2001)
10.4049/jimmunol.168.3.1356 / J. Immunol. (2002)
10.1073/pnas.95.13.7556 / Proc. Natl. Acad. Sci. USA. (1998)
10.1084/jem.20020063 / J. Exp. Med. (2002)
10.1084/jem.20021258 / J. Exp. Med. (2003)
10.1038/35074122 / Nature. (2001)
10.1084/jem.171.4.1269 / J. Exp. Med. (1990)
10.1084/jem.172.6.1877 / J. Exp. Med. (1990)
10.1146/annurev.immunol.20.100301.064812 / Annu. Rev. Immunol. (2002)
10.1034/j.1600-065X.2001.1810113.x / Immunol. Rev. (2001)
10.1093/intimm/13.4.459 / Int. Immunol. (2001)
10.1038/86297 / Nat. Immunol. (2001)
10.1126/science.1063916 / Science. (2001)
10.1038/344742a0 / Nature. (1990)
10.1006/cimm.1999.1536 / Cell. Immunol. (1999)
10.4049/jimmunol.157.2.941 / J. Immunol. (1996)
10.1073/pnas.90.20.9620 / Proc. Natl. Acad. Sci. USA. (1993)
10.1126/science.1853205 / Science. (1991)
10.4049/jimmunol.154.1.180 / J. Immunol. (1995)
10.4049/jimmunol.171.8.4020 / J. Immunol. (2003)
10.1136/gut.47.2.215 / Gut. (2000)
10.1038/35093109 / Nature. (2001)
10.1016/S0145-2126(00)00027-8 / Leuk. Res. (2000)
10.1084/jem.184.3.1149 / J. Exp. Med. (1996)
10.1084/jem.20021282 / J. Exp. Med. (2003)
10.1073/pnas.96.12.6879 / Proc. Natl. Acad. Sci. USA. (1999)
10.1084/jem.20030584 / J. Exp. Med. (2003)
10.1073/pnas.201238598 / Proc. Natl. Acad. Sci. USA. (2001)

Dates

Type	When
Created	21 years, 5 months ago (March 8, 2004, 8:53 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 8:35 a.m.)
Indexed	1 week ago (Aug. 24, 2025, 6:54 p.m.)
Issued	21 years, 5 months ago (March 8, 2004)
Published	21 years, 5 months ago (March 8, 2004)
Published Online	21 years, 5 months ago (March 8, 2004)
Published Print	21 years, 5 months ago (March 15, 2004)

Funders 0

None

BibTeX

@article{Street_2004, title={Innate Immune Surveillance of Spontaneous B Cell Lymphomas by Natural Killer Cells and γδ T Cells}, volume={199}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20031981}, DOI={10.1084/jem.20031981}, number={6}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Street, Shayna E.A. and Hayakawa, Yoshihiro and Zhan, Yifan and Lew, Andrew M. and MacGregor, Duncan and Jamieson, Amanda M. and Diefenbach, Andreas and Yagita, Hideo and Godfrey, Dale I. and Smyth, Mark J.}, year={2004}, month=mar, pages={879–884} }

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    {
      "key": "2023072512242101800_BIB2",
      "doi-asserted-by": "crossref",
      "first-page": "1611",
      "DOI": "10.1084/jem.188.9.1611",
      "volume": "188",
      "year": "1998",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB3",
      "doi-asserted-by": "crossref",
      "first-page": "661",
      "DOI": "10.1084/jem.191.4.661",
      "volume": "191",
      "year": "2000",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "2665",
      "DOI": "10.4049/jimmunol.165.5.2665",
      "volume": "165",
      "year": "2000",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512242101800_BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "755",
      "DOI": "10.1084/jem.192.5.755",
      "volume": "192",
      "year": "2000",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "6658",
      "DOI": "10.4049/jimmunol.162.11.6658",
      "volume": "162",
      "year": "1999",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512242101800_BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "192",
      "DOI": "10.1182/blood.V97.1.192",
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      "year": "2001",
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      "key": "2023072512242101800_BIB8",
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      "first-page": "1356",
      "DOI": "10.4049/jimmunol.168.3.1356",
      "volume": "168",
      "year": "2002",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512242101800_BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "7556",
      "DOI": "10.1073/pnas.95.13.7556",
      "volume": "95",
      "year": "1998",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072512242101800_BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "129",
      "DOI": "10.1084/jem.20020063",
      "volume": "196",
      "year": "2002",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB11",
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      "first-page": "1213",
      "DOI": "10.1084/jem.20021258",
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      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB12",
      "doi-asserted-by": "crossref",
      "first-page": "1107",
      "DOI": "10.1038/35074122",
      "volume": "410",
      "year": "2001",
      "journal-title": "Nature."
    },
    {
      "key": "2023072512242101800_BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "1269",
      "DOI": "10.1084/jem.171.4.1269",
      "volume": "171",
      "year": "1990",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "1877",
      "DOI": "10.1084/jem.172.6.1877",
      "volume": "172",
      "year": "1990",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "853",
      "DOI": "10.1146/annurev.immunol.20.100301.064812",
      "volume": "20",
      "year": "2002",
      "journal-title": "Annu. Rev. Immunol."
    },
    {
      "key": "2023072512242101800_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "158",
      "DOI": "10.1034/j.1600-065X.2001.1810113.x",
      "volume": "181",
      "year": "2001",
      "journal-title": "Immunol. Rev."
    },
    {
      "key": "2023072512242101800_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "459",
      "DOI": "10.1093/intimm/13.4.459",
      "volume": "13",
      "year": "2001",
      "journal-title": "Int. Immunol."
    },
    {
      "key": "2023072512242101800_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "293",
      "DOI": "10.1038/86297",
      "volume": "2",
      "year": "2001",
      "journal-title": "Nat. Immunol."
    },
    {
      "key": "2023072512242101800_BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "605",
      "DOI": "10.1126/science.1063916",
      "volume": "294",
      "year": "2001",
      "journal-title": "Science."
    },
    {
      "key": "2023072512242101800_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "742",
      "DOI": "10.1038/344742a0",
      "volume": "344",
      "year": "1990",
      "journal-title": "Nature."
    },
    {
      "key": "2023072512242101800_BIB21",
      "doi-asserted-by": "crossref",
      "first-page": "51",
      "DOI": "10.1006/cimm.1999.1536",
      "volume": "196",
      "year": "1999",
      "journal-title": "Cell. Immunol."
    },
    {
      "key": "2023072512242101800_BIB22",
      "doi-asserted-by": "crossref",
      "first-page": "941",
      "DOI": "10.4049/jimmunol.157.2.941",
      "volume": "157",
      "year": "1996",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512242101800_BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "9620",
      "DOI": "10.1073/pnas.90.20.9620",
      "volume": "90",
      "year": "1993",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072512242101800_BIB24",
      "doi-asserted-by": "crossref",
      "first-page": "199",
      "DOI": "10.1126/science.1853205",
      "volume": "253",
      "year": "1991",
      "journal-title": "Science."
    },
    {
      "key": "2023072512242101800_BIB25",
      "doi-asserted-by": "crossref",
      "first-page": "180",
      "DOI": "10.4049/jimmunol.154.1.180",
      "volume": "154",
      "year": "1995",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512242101800_BIB26",
      "doi-asserted-by": "crossref",
      "first-page": "4020",
      "DOI": "10.4049/jimmunol.171.8.4020",
      "volume": "171",
      "year": "2003",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512242101800_BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "215",
      "DOI": "10.1136/gut.47.2.215",
      "volume": "47",
      "year": "2000",
      "journal-title": "Gut."
    },
    {
      "key": "2023072512242101800_BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "165",
      "DOI": "10.1038/35093109",
      "volume": "413",
      "year": "2001",
      "journal-title": "Nature."
    },
    {
      "key": "2023072512242101800_BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "705",
      "DOI": "10.1016/S0145-2126(00)00027-8",
      "volume": "24",
      "year": "2000",
      "journal-title": "Leuk. Res."
    },
    {
      "key": "2023072512242101800_BIB30",
      "doi-asserted-by": "crossref",
      "first-page": "1149",
      "DOI": "10.1084/jem.184.3.1149",
      "volume": "184",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB31",
      "doi-asserted-by": "crossref",
      "first-page": "747",
      "DOI": "10.1084/jem.20021282",
      "volume": "198",
      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB32",
      "doi-asserted-by": "crossref",
      "first-page": "6879",
      "DOI": "10.1073/pnas.96.12.6879",
      "volume": "96",
      "year": "1999",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072512242101800_BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "433",
      "DOI": "10.1084/jem.20030584",
      "volume": "198",
      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512242101800_BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "11521",
      "DOI": "10.1073/pnas.201238598",
      "volume": "98",
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