Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression.

Abstract

SummaryThe immune response against lymphocytic choriomeningitis virus (LCMV) was studied in a mutant mouse strain that does not possess CD8 § T lymphocytes. Virus-specific cytotoxic T cell activity was generated in spleens of wild-type mice in an acute LCMV infection but was not measurable in mutant mice. Injection of replicating LCMV into footpads of wild-type mice induced a CD8 + T cell-mediated swelling that peaked on day 8, followed by a CD4 + T cell-mediated swelling that peaked on day 11, whereas mutant mice exhibited only the CD4 + T cell-mediated swelling. After intracerebral inoculation with LCMV-Armstrong, all wild-type mice died of classical CD8 § T cell-dependent choriomeningitis in 8-10 days. Mutant mice showed symptoms of general malaise but most of them survived. Mutant mice depleted of CD4 § T cells by monoclonal antibody treatment showed no clinical signs of sickness. On day 9 after intravenous infection with LCMV-WE, virus was detected at high titers in spleens and livers of mutant mice but not in those of wild-type mice. On day 70 after injection of LCMV-WE into footpads, virus was not detected in wild-type mice and in one of the three mutant mice tested, but was still measurable in kidneys of the other two mutant mice. These results confirm in a new animal model that CD8 § T cell-mediated immunity is crucial in LCMV clearance and in the immunopathological disease during LCMV infection. In addition, our results demonstrated a less severe form of choriomeningitis mediated by CD4 + T cells and slow clearance of LCMV by alternative pathways independent of CD8 + T cells. C D8 T cells play an essential role in the immune response in mice against lymphocytic choriomeningitis virus (LCMV), 1 whereas antibodies of CD4 + T cells do not seem to be crucially involved (1-4). A virus-specific cytotoxic activity mediated by CD8* T cells is generated in mice 7-9 d after an acute LCMV infection (5). CD8 + T cells cause a swelling reaction 6-8 d after injection of replicating LCMV into footpads, whereas CD4 * T cells are involved in the later phase of the swelling (6, 7). Intracerebral injection of LCMV into immunocompetent mice causes-a fatal choriomeningitis that has been demonstrated to be mediated by CTL (8,9). The respective roles of CD8 + and CD4 § T cells against LCMV infection have so far been studied in adoptive transfer experiments (2-4) and in vivo depletion experiments with mAbs against CD8 and CD4 (10-12). We have now generated a mutant mouse without CD8 expres- sion by disrupting the Lyt-2 gene, which encodes one subunit of the CD8 heterodimer, with the technology of homologous recombination in embryonic stem cells (13). In this mouse strain, it has not been possible to demonstrate the presence of class I MHC-restricted cytotoxic T cells. For the study of the consequences of the anti-LCMV immune response without CD8 + T cells, this new mouse model has several advantages compared to in vivo depletion experiments with mAbs. The mutant mice are devoid of CD8 § T cells, and possible problems arising ...

Phenotypic and functional evaluation of CD3+CD4-CD8- T cells in human CD8 immunodeficiency

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The IL-33/ST2 Pathway Controls Coxsackievirus B5–Induced Experimental Pancreatitis

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PD-1:PD-L1 Interactions Contribute to the Functional Suppression of Virus-Specific CD8+ T Lymphocytes in the Liver

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