DOI: 10.1084/jem.20040317. The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation

The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation

10.1084/jem.20040317

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied α-galactosylceramide. This glycolipid activates innate Vα14+ natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)–α and interferon (IFN)-γ were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40−/− and CD40L−/− mice did not elicit CD4+ and CD8+ T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-α up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40−/− mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation (“signal one”) and costimulation (“signal two”) to generate functioning CD4+ T helper cell 1 and CD8+ cytolytic T lymphocytes.

Bibliography

Fujii, S., Liu, K., Smith, C., Bonito, A. J., & Steinman, R. M. (2004). The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation. The Journal of Experimental Medicine, 199(12), 1607â1618.

Authors 5

Shin-ichiro Fujii (first)
Kang Liu (additional)
Caroline Smith (additional)
Anthony J. Bonito (additional)
Ralph M. Steinman (additional)

References 57 Referenced 482

10.1146/annurev.immunol.19.1.47 / Annu. Rev. Immunol. (2001)
10.1016/S1074-7613(03)00182-1 / Immunity. (2003)
10.1073/pnas.231606698 / Proc. Natl. Acad. Sci. USA. (2002)
10.1084/jem.184.4.1413 / J. Exp. Med. (1996)
10.1002/1521-4141(200012)30:12<3591::AID-IMMU3591>3.0.CO;2-J / Eur. J. Immunol. (2000)
10.4049/jimmunol.165.12.6762 / J. Immunol. (2000)
10.1084/jem.20020161 / J. Exp. Med. (2002)
10.1084/jem.20021215 / J. Exp. Med. (2002)
10.1084/jem.194.6.769 / J. Exp. Med. (2001)
10.1084/jem.20021598 / J. Exp. Med. (2002)
10.1182/blood-2003-02-0513 / Blood. (2003)
{'key': '2023072512215819700_BIB12', 'volume': 'In press', 'year': '2004', 'journal-title': 'Immunity.'} / Immunity. (2004)
10.1084/jem.20030422 / J. Exp. Med. (2003)
10.1084/jem.20030266 / J. Exp. Med. (2003)
10.1084/jem.20030324 / J. Exp. Med. (2003)
10.4049/jimmunol.171.10.5140 / J. Immunol. (2003)
10.1084/jem.20032220 / J. Exp. Med. (2004)
10.1126/science.278.5343.1626 / Science. (1997)
10.1084/jem.20011889 / J. Exp. Med. (2002)
10.1084/jem.20030645 / J. Exp. Med. (2003)
10.1084/jem.180.4.1263 / J. Exp. Med. (1994)
10.1084/jem.185.2.341 / J. Exp. Med. (1997)
10.1084/jem.20021542 / J. Exp. Med. (2003)
10.4049/jimmunol.168.3.1172 / J. Immunol. (2002)
10.1084/jem.184.2.747 / J. Exp. Med. (1996)
10.1084/jem.184.2.741 / J. Exp. Med. (1996)
10.1038/30989 / Nature. (1998)
10.1038/30996 / Nature. (1998)
10.1038/31002 / Nature. (1998)
{'key': '2023072512215819700_BIB30'}
10.1084/jem.179.4.1109 / J. Exp. Med. (1994)
10.1084/jem.191.6.927 / J. Exp. Med. (2000)
10.1016/S1074-7613(01)00126-1 / Immunity. (2001)
10.1084/jem.192.5.741 / J. Exp. Med. (2000)
10.4049/jimmunol.166.9.5448 / J. Immunol. (2001)
10.1006/cimm.1999.1602 / Cell. Immunol. (2000)
10.1073/pnas.1332805100 / Proc. Natl. Acad. Sci. USA. (2003)
10.4049/jimmunol.163.1.93 / J. Immunol. (1999)
10.1038/82161 / Nat. Med. (2000)
10.1084/jem.186.1.65 / J. Exp. Med. (1997)
10.1016/S1074-7613(00)00045-5 / Immunity. (2000)
10.4049/jimmunol.169.7.3652 / J. Immunol. (2002)
10.4049/jimmunol.171.12.6406 / J. Immunol. (2003)
10.1084/jem.192.1.145 / J. Exp. Med. (2000)
10.1084/jem.161.3.526 / J. Exp. Med. (1985)
10.1084/jem.164.2.605 / J. Exp. Med. (1986)
10.1084/jem.169.3.1169 / J. Exp. Med. (1989)
10.1084/jem.169.3.1153 / J. Exp. Med. (1989)
10.1038/ni722 / Nat. Immunol. (2001)
10.1038/35393 / Nature. (1998)
10.1038/nm962 / Nat. Med. (2003)
10.1084/jem.191.3.495 / J. Exp. Med. (2000)
10.1084/jem.191.11.2011 / J. Exp. Med. (2000)
10.1016/S1074-7613(03)00327-3 / Immunity. (2003)
10.4049/jimmunol.166.1.277 / J. Immunol. (2001)
10.4049/jimmunol.162.1.168 / J. Immunol. (1999)
10.4049/jimmunol.167.11.6247 / J. Immunol. (2001)

Dates

Type	When
Created	21 years, 2 months ago (June 15, 2004, 2:28 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 8:32 a.m.)
Indexed	1 week, 3 days ago (Aug. 20, 2025, 8:43 a.m.)
Issued	21 years, 2 months ago (June 14, 2004)
Published	21 years, 2 months ago (June 14, 2004)
Published Online	21 years, 2 months ago (June 14, 2004)
Published Print	21 years, 2 months ago (June 21, 2004)

Funders 0

None

BibTeX

@article{Fujii_2004, title={The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation}, volume={199}, ISSN={0022-1007}, url={http://dx.doi.org/10.1084/jem.20040317}, DOI={10.1084/jem.20040317}, number={12}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Fujii, Shin-ichiro and Liu, Kang and Smith, Caroline and Bonito, Anthony J. and Steinman, Ralph M.}, year={2004}, month=jun, pages={1607–1618} }

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  "abstract": "<jats:p>Dendritic cell (DC) maturation is an innate response that leads to adaptive immunity to coadministered proteins. To begin to identify underlying mechanisms in intact lymphoid tissues, we studied \u03b1-galactosylceramide. This glycolipid activates innate V\u03b114+ natural killer T cell (NKT) lymphocytes, which drive DC maturation and T cell responses to ovalbumin antigen. Hours after giving glycolipid i.v., tumor necrosis factor (TNF)\u2013\u03b1 and interferon (IFN)-\u03b3 were released primarily by DCs. These cytokines induced rapid surface remodeling of DCs, including increased CD80/86 costimulatory molecules. Surprisingly, DCs from CD40\u2212/\u2212 and CD40L\u2212/\u2212 mice did not elicit CD4+ and CD8+ T cell immunity, even though the DCs exhibited presented ovalbumin on major histocompatibility complex class I and II products and expressed high levels of CD80/86. Likewise, an injection of TNF-\u03b1 up-regulated CD80/86 on DCs, but CD40 was required for immunity. CD40 was needed for DC interleukin (IL)-12 production, but IL-12p40\u2212/\u2212 mice generated normal ovalbumin-specific responses. Therefore, the link between innate and adaptive immunity via splenic DCs and innate NKT cells has several components under distinct controls: antigen presentation in the steady state, increases in costimulatory molecules dependent on inflammatory cytokines, and a distinct CD40/CD40L signal that functions together with antigen presentation (\u201csignal one\u201d) and costimulation (\u201csignal two\u201d) to generate functioning CD4+ T helper cell 1 and CD8+ cytolytic T lymphocytes.</jats:p>",
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      "DOI": "10.1016/S1074-7613(03)00182-1",
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      "year": "2003",
      "journal-title": "Immunity."
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    {
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      "first-page": "351",
      "DOI": "10.1073/pnas.231606698",
      "volume": "99",
      "year": "2002",
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    },
    {
      "key": "2023072512215819700_BIB4",
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      "DOI": "10.1084/jem.184.4.1413",
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    },
    {
      "key": "2023072512215819700_BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "3591",
      "DOI": "10.1002/1521-4141(200012)30:12<3591::AID-IMMU3591>3.0.CO;2-J",
      "volume": "30",
      "year": "2000",
      "journal-title": "Eur. J. Immunol."
    },
    {
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      "first-page": "6762",
      "DOI": "10.4049/jimmunol.165.12.6762",
      "volume": "165",
      "year": "2000",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512215819700_BIB7",
      "doi-asserted-by": "crossref",
      "first-page": "1289",
      "DOI": "10.1084/jem.20020161",
      "volume": "195",
      "year": "2002",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB8",
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      "first-page": "1091",
      "DOI": "10.1084/jem.20021215",
      "volume": "196",
      "year": "2002",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB9",
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      "first-page": "769",
      "DOI": "10.1084/jem.194.6.769",
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      "first-page": "1627",
      "DOI": "10.1084/jem.20021598",
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      "year": "2002",
      "journal-title": "J. Exp. Med."
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      "first-page": "2187",
      "DOI": "10.1182/blood-2003-02-0513",
      "volume": "102",
      "year": "2003",
      "journal-title": "Blood."
    },
    {
      "key": "2023072512215819700_BIB12",
      "volume": "In press",
      "year": "2004",
      "journal-title": "Immunity."
    },
    {
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      "first-page": "235",
      "DOI": "10.1084/jem.20030422",
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      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "133",
      "DOI": "10.1084/jem.20030266",
      "volume": "198",
      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "267",
      "DOI": "10.1084/jem.20030324",
      "volume": "198",
      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "5140",
      "DOI": "10.4049/jimmunol.171.10.5140",
      "volume": "171",
      "year": "2003",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512215819700_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "815",
      "DOI": "10.1084/jem.20032220",
      "volume": "199",
      "year": "2004",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "1626",
      "DOI": "10.1126/science.278.5343.1626",
      "volume": "278",
      "year": "1997",
      "journal-title": "Science."
    },
    {
      "key": "2023072512215819700_BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "617",
      "DOI": "10.1084/jem.20011889",
      "volume": "195",
      "year": "2002",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "281",
      "DOI": "10.1084/jem.20030645",
      "volume": "198",
      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB21",
      "doi-asserted-by": "crossref",
      "first-page": "1263",
      "DOI": "10.1084/jem.180.4.1263",
      "volume": "180",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB22",
      "doi-asserted-by": "crossref",
      "first-page": "341",
      "DOI": "10.1084/jem.185.2.341",
      "volume": "185",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "111",
      "DOI": "10.1084/jem.20021542",
      "volume": "198",
      "year": "2003",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB24",
      "doi-asserted-by": "crossref",
      "first-page": "1172",
      "DOI": "10.4049/jimmunol.168.3.1172",
      "volume": "168",
      "year": "2002",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512215819700_BIB25",
      "doi-asserted-by": "crossref",
      "first-page": "747",
      "DOI": "10.1084/jem.184.2.747",
      "volume": "184",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB26",
      "doi-asserted-by": "crossref",
      "first-page": "741",
      "DOI": "10.1084/jem.184.2.741",
      "volume": "184",
      "year": "1996",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "474",
      "DOI": "10.1038/30989",
      "volume": "393",
      "year": "1998",
      "journal-title": "Nature."
    },
    {
      "key": "2023072512215819700_BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "478",
      "DOI": "10.1038/30996",
      "volume": "393",
      "year": "1998",
      "journal-title": "Nature."
    },
    {
      "key": "2023072512215819700_BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "480",
      "DOI": "10.1038/31002",
      "volume": "393",
      "year": "1998",
      "journal-title": "Nature."
    },
    {
      "key": "2023072512215819700_BIB30"
    },
    {
      "key": "2023072512215819700_BIB31",
      "doi-asserted-by": "crossref",
      "first-page": "1109",
      "DOI": "10.1084/jem.179.4.1109",
      "volume": "179",
      "year": "1994",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB32",
      "doi-asserted-by": "crossref",
      "first-page": "927",
      "DOI": "10.1084/jem.191.6.927",
      "volume": "191",
      "year": "2000",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "461",
      "DOI": "10.1016/S1074-7613(01)00126-1",
      "volume": "14",
      "year": "2001",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072512215819700_BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "741",
      "DOI": "10.1084/jem.192.5.741",
      "volume": "192",
      "year": "2000",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB35",
      "doi-asserted-by": "crossref",
      "first-page": "5448",
      "DOI": "10.4049/jimmunol.166.9.5448",
      "volume": "166",
      "year": "2001",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512215819700_BIB36",
      "doi-asserted-by": "crossref",
      "first-page": "37",
      "DOI": "10.1006/cimm.1999.1602",
      "volume": "199",
      "year": "2000",
      "journal-title": "Cell. Immunol."
    },
    {
      "key": "2023072512215819700_BIB37",
      "doi-asserted-by": "crossref",
      "first-page": "8395",
      "DOI": "10.1073/pnas.1332805100",
      "volume": "100",
      "year": "2003",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072512215819700_BIB38",
      "doi-asserted-by": "crossref",
      "first-page": "93",
      "DOI": "10.4049/jimmunol.163.1.93",
      "volume": "163",
      "year": "1999",
      "journal-title": "J. Immunol."
    },
    {
      "key": "2023072512215819700_BIB39",
      "doi-asserted-by": "crossref",
      "first-page": "1348",
      "DOI": "10.1038/82161",
      "volume": "6",
      "year": "2000",
      "journal-title": "Nat. Med."
    },
    {
      "key": "2023072512215819700_BIB40",
      "doi-asserted-by": "crossref",
      "first-page": "65",
      "DOI": "10.1084/jem.186.1.65",
      "volume": "186",
      "year": "1997",
      "journal-title": "J. Exp. Med."
    },
    {
      "key": "2023072512215819700_BIB41",
      "doi-asserted-by": "crossref",
      "first-page": "453",
      "DOI": "10.1016/S1074-7613(00)00045-5",
      "volume": "13",
      "year": "2000",
      "journal-title": "Immunity."
    },
    {
      "key": "2023072512215819700_BIB42",
      "doi-asserted-by": "crossref",
      "first-page": "3652",
      "DOI": "10.4049/jimmunol.169.7.3652",
      "volume": "169",
      "year": "2002",
      "journal-title": "J. Immunol."
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