Lymphocytic Choriomeningitis Virus

Lehmann-Grube, F

doi:10.1016/b978-0-12-262502-2.50019-5

Cited by 41 publications

(68 citation statements)

References 236 publications

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“…(13). LCMV is a noncytopathic single-stranded RNA virus from the arena virus family (14). Several different strains of LCMV have been isolated, some of which cause systemic infection by interacting with a broad variety of cells, possibly, as has been shown in vitro, via the highly conserved membrane protein ␣-dystroglycan (15).…”

Section: Ntestinal Intraepithelial Lymphocytes (Iel)mentioning

confidence: 99%

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Intestinal Intraepithelial Lymphocytes Exert Potent Protective Cytotoxic Activity During an Acute Virus Infection

Müller

Bühler-Jungo

Mueller

2000

The Journal of Immunology

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After systemic infection of mice with 104 PFU of lymphocytic choriomeningitis virus (LCMV), infected cells are detected simultaneously in various organs, including spleen and intestinal mucosa. Most notably, virus-infected cells are also present among CD11c+ dendritic cells in the subepithelial area of the small intestinal mucosa. Some of these virus-infected cells are in close spatial association with intestinal intraepithelial lymphocytes (IEL). Therefore, we compared virus-specific cytotoxic activity of CD8 splenocytes with that of IEL subsets. While ex vivo isolated TCRαβ+CD8αα+ IEL exert only minimal virus-specific cytotoxicity, maximum specific killing mediated by TCRαβ+CD8αβ+ IEL on day 8 postinfection exceeds maximum cytotoxic activity observed with CD8 splenocytes when assessed in vitro. Maximum cytotoxic activity of IEL is preceded by peak perforin and granzyme B mRNA expression in IEL around day 6 postinfection, suggesting a recent activation in situ. The antivirus cytotoxicity of in vivo primed IEL is further demonstrated by the protection from virus production in the spleen of mice infected with LCMV 10 h before adoptive cell transfer. These data indicate a potent priming of LCMV-specific IEL in situ after systemic LCMV infection and suggest that cytotoxic IEL markedly contribute to the elimination of virus-infected cells in the intestinal mucosa.

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Section: Ntestinal Intraepithelial Lymphocytes (Iel)mentioning

confidence: 99%

“…A stock of LCMV strain WE (14) was provided by S. Oehen (Zurich, Switzerland). Unless otherwise indicated, 10 4 PFU of LCMV-WE/mouse in a volume of 100 l of MEM and 2% FCS was injected i.p.…”

Section: Lcmv Infectionsmentioning

confidence: 99%

Intestinal Intraepithelial Lymphocytes Exert Potent Protective Cytotoxic Activity During an Acute Virus Infection

Müller

Bühler-Jungo

Mueller

2000

The Journal of Immunology

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“…The LCMV-WE strain was originally obtained from F. Lehmann-Grube (Hamburg, Germany) (32). The virus was grown and titrated on L929 cells, and virus stocks were stored at Ϫ70°C.…”

Section: Virusesmentioning

confidence: 99%

The Selective Proteasome Inhibitors Lactacystin and Epoxomicin Can Be Used to Either Up- or Down-Regulate Antigen Presentation at Nontoxic Doses

Schwarz

Giuli

Schmidtke

et al. 2000

The Journal of Immunology

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The complete inhibition of proteasome activities interferes with the production of most MHC class I peptide ligands as well as with cellular proliferation and survival. In this study we have investigated how partial and selective inhibition of the chymotrypsin-like activity of the proteasome by the proteasome inhibitors lactacystin or epoxomicin would affect Ag presentation. At 0.5–1 μM lactacystin, the presentation of the lymphocytic choriomeningitis virus-derived epitopes NP118 and GP33 and the mouse CMV epitope pp89–168 were reduced and were further diminished in a dose-dependent manner with increasing concentrations. Presentation of the lymphocytic choriomeningitis virus-derived epitope GP276, in contrast, was markedly enhanced at low, but abrogated at higher, concentrations of either lactacystin or epoxomicin. The inhibitor-mediated effects were thus epitope specific and did not correlate with the degradation rates of the involved viral proteins. Although neither apoptosis induction nor interference with cellular proliferation was observed at 0.5–1 μM lactacystin in vivo, this concentration was sufficient to alter the fragmentation of polypeptides by the 20S proteasome in vitro. Our results indicate that partial and selective inhibition of proteasome activity in vivo is a valid approach to modulate Ag presentation, with potential applications for the treatment of autoimmune diseases and the prevention of transplant rejection.

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“…BRIEF DEFINITIVE REPORT Virus. The LCMVWE strain was originally obtained from Dr. F. Lehmann-Grube, Hamburg, FRG, and was grown in L929 fibroblast cells (12). The vaccinia virus WR strain was grown in BSC-1 cells .…”

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confidence: 99%

Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.

Aichele

Hengartner

Zinkernagel

et al. 1990

The Journal of Experimental Medicine

190

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Antiviral cytotoxic T lymphocytes (CTL) are specifically induced against viral antigens presented by MHC class I molecules on the surface of infected cells (1). The intracellularly synthesized antigens are processed and associated with class I antigens within cells in a yet poorly defined way before presentation on the cell surface (2). Induced effector CTL also recognize synthetic peptides bound by MHC class I molecules from without on the cell surface in absence of an apparent need for cell internal processing (3, 4).Virus-specific CTL have been shown to be crucially involved in recovery from and in protection against lymphocytic choriomeningitis virus (LCMV) (5) and many other virus infections . Induction ofCTL response is best achieved in vivo by priming with replicating virus. Since vaccination with live virus may cause, although rarely, some disease, means have been sought for many years to induce virus-specific CTL responses in vivo with nonreplicating synthetic virus antigens .In the past few years in vivo priming of class I-restricted T cells with free proteins or peptides was shown for ovalbumin with whole soluble protein (6) or tryptic digests of the whole protein or relatively large peptides of the relevant T cell epitope ofovalbumin (7,8). Recently it was shown that short synthetic peptides of influenza virus nucleoprotein can induce specific responses in vivo to the priming peptide as well as to the virus; induction was possible with chemically modified peptides linked to a lipid component but not with free peptides (9).We evaluated whether the free unmodified 15-mer peptide (RPQASGVYMGN-LTAQ) representing a H-2a T cell epitope of LCMV nucleoprotein (10, 11) could induce in vivo a specific CTL response to LCMV and we report on the successful demonstration ofsuch a response. Although stringently restricted to the class I MHC allele for the peptide used, these results demonstrate the feasibility ofusing unmodified T cell epitope peptides as antiviral vaccines in principal .

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Lymphocytic Choriomeningitis Virus

Cited by 41 publications

References 236 publications

Intestinal Intraepithelial Lymphocytes Exert Potent Protective Cytotoxic Activity During an Acute Virus Infection

Intestinal Intraepithelial Lymphocytes Exert Potent Protective Cytotoxic Activity During an Acute Virus Infection

The Selective Proteasome Inhibitors Lactacystin and Epoxomicin Can Be Used to Either Up- or Down-Regulate Antigen Presentation at Nontoxic Doses

Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.

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