Lymphotoxin-β-deficient mice show defective antiviral immunity

Dietmar P. Berger; Denise Naniche; Mary T. Crowley; Pandelakis A. Koni; Richard A. Flavell; Michael B.A. Oldstone

doi:10.1006/viro.1999.9811

Lymphotoxin-β-deficient mice show defective antiviral immunity

Dietmar P. Berger, Denise Naniche, Mary T. Crowley, Pandelakis A. Koni, Richard A. Flavell, Michael B.A. Oldstone

Infectious Disease

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

Abstract

Lymphotoxin β (LTβ), a member of the tumor necrosis factor family, plays an important role in lymphoid organogenesis. In order to determine whether LTβ is involved in cellular immunity, we investigated the antiviral immune response of LTβ-deficient (LTβ -/-) mice to lymphocytic choriomeningitis virus (LCMV). Cytotoxic T lymphocyte (CTL) responses to LCMV were severely diminished, leading to viral persistence in brain and kidney. However, major functions of LTβ-deficient T lymphocytes and dendritic cells were intact. Reconstitution of irradiated LTβ +/+ mice with LTβ -/- bone marrow induced a disorganized splenic structure, accompanied by impairment of the LCMV-specific CTL response. These data indicate that the absence of LTβ does not affect the intrinsic function of T lymphocytes or of dendritic cells but that the structural integrity of the spleen is strongly associated with generation of antiviral immunity.

Original language	English (US)
Pages (from-to)	136-147
Number of pages	12
Journal	Virology
Volume	260
Issue number	1
DOIs	https://doi.org/10.1006/viro.1999.9811
State	Published - Jul 20 1999

Keywords

CTL
Cell surface molecules
Dendritic cells
Lymphoid organization

ASJC Scopus subject areas

Virology

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10.1006/viro.1999.9811

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title = "Lymphotoxin-β-deficient mice show defective antiviral immunity",

abstract = "Lymphotoxin β (LTβ), a member of the tumor necrosis factor family, plays an important role in lymphoid organogenesis. In order to determine whether LTβ is involved in cellular immunity, we investigated the antiviral immune response of LTβ-deficient (LTβ -/-) mice to lymphocytic choriomeningitis virus (LCMV). Cytotoxic T lymphocyte (CTL) responses to LCMV were severely diminished, leading to viral persistence in brain and kidney. However, major functions of LTβ-deficient T lymphocytes and dendritic cells were intact. Reconstitution of irradiated LTβ +/+ mice with LTβ -/- bone marrow induced a disorganized splenic structure, accompanied by impairment of the LCMV-specific CTL response. These data indicate that the absence of LTβ does not affect the intrinsic function of T lymphocytes or of dendritic cells but that the structural integrity of the spleen is strongly associated with generation of antiviral immunity.",

keywords = "CTL, Cell surface molecules, Dendritic cells, Lymphoid organization",

author = "Berger, {Dietmar P.} and Denise Naniche and Crowley, {Mary T.} and Koni, {Pandelakis A.} and Flavell, {Richard A.} and Oldstone, {Michael B.A.}",

note = "Funding Information: We thank Dirk Homann for assistance with CD8+ T cell enrichment. We also acknowledge David Lo for assistance in the dendritic cell purification. This work was supported by U.S. Public Health Grant AI09484, by NIH Training Grant AG00080 (D.N.), by a fellowship from the Deutsche Forschungsgemeinschaft, Be1702/1-1 (D.P.B.), by USPHS Grant AI38375, and by a grant from the International Human Frontier Science Program (M.T.C.). Richard A. Flavell is an investigator of the Howard Hughes Medical Institute with support from the American Diabetes Association for Pandelakis A. Koni.",

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AU - Flavell, Richard A.

AU - Oldstone, Michael B.A.

N1 - Funding Information: We thank Dirk Homann for assistance with CD8+ T cell enrichment. We also acknowledge David Lo for assistance in the dendritic cell purification. This work was supported by U.S. Public Health Grant AI09484, by NIH Training Grant AG00080 (D.N.), by a fellowship from the Deutsche Forschungsgemeinschaft, Be1702/1-1 (D.P.B.), by USPHS Grant AI38375, and by a grant from the International Human Frontier Science Program (M.T.C.). Richard A. Flavell is an investigator of the Howard Hughes Medical Institute with support from the American Diabetes Association for Pandelakis A. Koni.

PY - 1999/7/20

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N2 - Lymphotoxin β (LTβ), a member of the tumor necrosis factor family, plays an important role in lymphoid organogenesis. In order to determine whether LTβ is involved in cellular immunity, we investigated the antiviral immune response of LTβ-deficient (LTβ -/-) mice to lymphocytic choriomeningitis virus (LCMV). Cytotoxic T lymphocyte (CTL) responses to LCMV were severely diminished, leading to viral persistence in brain and kidney. However, major functions of LTβ-deficient T lymphocytes and dendritic cells were intact. Reconstitution of irradiated LTβ +/+ mice with LTβ -/- bone marrow induced a disorganized splenic structure, accompanied by impairment of the LCMV-specific CTL response. These data indicate that the absence of LTβ does not affect the intrinsic function of T lymphocytes or of dendritic cells but that the structural integrity of the spleen is strongly associated with generation of antiviral immunity.

AB - Lymphotoxin β (LTβ), a member of the tumor necrosis factor family, plays an important role in lymphoid organogenesis. In order to determine whether LTβ is involved in cellular immunity, we investigated the antiviral immune response of LTβ-deficient (LTβ -/-) mice to lymphocytic choriomeningitis virus (LCMV). Cytotoxic T lymphocyte (CTL) responses to LCMV were severely diminished, leading to viral persistence in brain and kidney. However, major functions of LTβ-deficient T lymphocytes and dendritic cells were intact. Reconstitution of irradiated LTβ +/+ mice with LTβ -/- bone marrow induced a disorganized splenic structure, accompanied by impairment of the LCMV-specific CTL response. These data indicate that the absence of LTβ does not affect the intrinsic function of T lymphocytes or of dendritic cells but that the structural integrity of the spleen is strongly associated with generation of antiviral immunity.

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Lymphotoxin-β-deficient mice show defective antiviral immunity

Abstract

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