Altered tissue distribution of viral replication and T cell spreading is pivotal in the protection against fatal lymphocytic choriomeningitis in mice after neutralization of IFN-alpha/beta.

Abstract

IFN-alpha/beta have been shown to play a central role in the development of lymphocytic choriomeningitis and increasing attention has been focused on this group of cytokines as early regulatory factors directing T lymphocyte responses. In the present study, injection of antiserum to IFN-alpha/beta prevented the development of lymphocytic choriomeningitis, was associated with the absence of detectable expression of early 2'-5' oligo-adenylate synthetase mRNA and coincided with viremia of lymphocytic choriomeningitis virus (LCMV) followed by establishment of a persistent infection. The LCMV-specific cytotoxic T lymphocyte response was unchanged in cervical lymph nodes but decreased in the spleen of anti-IFN-alpha/beta-treated animals. The expression of cytokine mRNA (particularly IFN-gamma) in organs of LCMV-infected mice treated with anti-IFN-alpha/beta coincided with infiltration of lymphocytes and tissue destruction. Furthermore, a reduced number of infiltrating leukocytes in the brain and cervical lymph nodes and a low expression of cytokine mRNA in the brain was observed in anti-IFN-alpha/beta-treated animals. In total, the findings support the view that neutralization of IFN-alpha/beta leads to extensive LCMV replication in the viscera. The therapeutic effects of anti-IFN-alpha/beta antiserum seem to be independent of the functional capacity of T cells but probably result in a dispersion of activated T cells throughout the body of LCMV-infected mice. Absence of IFN-alpha/beta expression in the central nervous system is proposed as the mechanism behind the IFN-alpha/beta-dependent targeting of T cells to the brain.

• Authors: K Sandberg, P Kemper, A Stalder, J Zhang, M V Hobbs, J L Whitton, I L Campbell
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 153 Issue 1 Pg. 220-31 (Jul 01 1994) ISSN: 0022-1767 [Print] United States
• PMID: 8207238 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• Interferon Type I
• RNA, Messenger
• 2',5'-Oligoadenylate Synthetase

Topics

• 2',5'-Oligoadenylate Synthetase (genetics)
• Animals
• Antigen-Antibody Reactions
• CD4-CD8 Ratio
• Cell Adhesion
• Cytokines (genetics)
• Cytotoxicity, Immunologic
• Gene Expression
• Interferon Type I (antagonists & inhibitors, immunology)
• Lymphocyte Activation
• Lymphocytic Choriomeningitis (immunology, microbiology, prevention & control)
• Lymphocytic choriomeningitis virus (growth & development)
• Male
• Mice
• Mice, Inbred BALB C
• RNA, Messenger (genetics)
• T-Lymphocytes (cytology, microbiology)
• Tissue Distribution
• Virus Replication