Resistance of naive mice to murine hepatitis virus strain 3 requires development of a Th1, but not a Th2, response, whereas pre-existing antibody partially protects against primary infection.

Abstract

Murine hepatitis virus strain 3 (MHV-3) produces a strain-dependent spectrum of disease. The development of liver necrosis has been shown to be related to production of a unique macrophage procoagulant activity (PCA), encoded by the gene fgl-2, in susceptible mice. These studies were designed to examine the influence of Th1/Th2 cells on resistance/susceptibility and production of macrophage PCA in resistant (A/J) and susceptible (BALB/cJ) strains of mice following infection with MHV-3. Immunization of A/J mice with MHV-3 induced a Th1 cellular immune response, and one Th1 cell line (3E9.1) protected susceptible mice and inhibited PCA production by macrophages both in vitro and in vivo. In contrast, immunization of BALB/cJ mice with an attenuated variant of MHV-3 derived from passaging MHV-3 in YAC-1 cells resulted in a Th2 response. Transfer of spleen cells and T cell lines from immunized BALB/cJ mice failed to protect naive susceptible syngeneic mice from infection with MHV-3 and augmented macrophage PCA production to MHV-3 in vitro. However, serum from immunized BALB/cJ mice contained high titrated neutralizing Ab that protected naive BALB/cJ animals from lethal primary MHV-3 infection. These results demonstrate that susceptible BALB/cJ mice generate a Th2 response following MHV-3 infection and that these Th2 cells neither inhibit MHV-3-induced macrophage PCA production nor protect naive mice from MHV-3 infection. The results suggest that Ab protects against primary infection but cannot eradicate ongoing infection. Thus, these data define the differential role of Th1/Th2 lymphocytes in primary and secondary MHV-3 infection and emphasize the importance of PCA in the pathogenesis of MHV-3 infection.

• Authors: M Pope, S W Chung, T Mosmann, J L Leibowitz, R M Gorczynski, G A Levy
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 156 Issue 9 Pg. 3342-9 (May 01 1996) ISSN: 0022-1767 [Print] United States
• PMID: 8617959 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Viral
• Blood Coagulation Factors
• Viral Vaccines
• macrophage procoagulant activity

Topics

• Animals
• Antibodies, Viral (therapeutic use)
• Blood Coagulation Factors (biosynthesis, immunology)
• Cell Line
• Coronavirus Infections (immunology)
• Disease Susceptibility
• Female
• Hepatitis, Viral, Animal (immunology, prevention & control)
• Immunity, Innate
• Immunization, Passive
• Immunotherapy, Adoptive
• Macrophages (immunology)
• Mice
• Mice, Inbred A
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Murine hepatitis virus (immunology)
• Spleen (transplantation)
• Th1 Cells (immunology, virology)
• Th2 Cells (immunology, virology)
• Viral Vaccines (immunology)