Cellular immunity in chronic Theiler's virus central nervous system infection

Area of Science:

• Neuroimmunology
• Virology
• Immunology

Background:

• SJL/J mice infected with the DA strain of Theiler's Murine Encephalomyelitis Virus (TMEV) develop chronic central nervous system (CNS) infections.
• This chronic infection is characterized by inflammation, mononuclear cell infiltration in the spinal cord, and demyelination.

Purpose of the Study:

• To investigate the temporal dynamics of cell-mediated and humoral immune responses during chronic TMEV infection in mice.
• To characterize the nature of the spleen cell reactivity against TMEV antigens.

Main Methods:

• Mice were inoculated with TMEV, and immune responses were monitored over time.
• In vitro assays measured spleen cell proliferation (3H-TdR incorporation) in response to inactivated TMEV antigen.
• Humoral immunity was assessed by measuring serum-neutralizing antibodies.
• Responses to mitogens and heterologous antigens (sheep red blood cells) were evaluated to assess general immune function.

Main Results:

• Immunologically specific spleen cell reactivity to TMEV antigen was detected approximately 2 months post-infection and persisted for over a year.
• This spleen cell reactivity correlated with the development of serum-neutralizing antibodies.
• The immune response was not due to general immunosuppression, as mice showed normal responses to mitogens and foreign antigens.
• Antiviral antibodies were found to inhibit virus-induced spleen cell reactivity.
• The antigen-reactive lymphocytes in the spleen were identified as T cells, not B cells.

Conclusions:

• Chronic TMEV infection induces a specific and long-lasting T cell-mediated immune response in the spleen.
• The development of this T cell response is not impaired by immunosuppression and is influenced by antiviral antibodies.
• These findings elucidate the adaptive immune mechanisms underlying chronic viral infections of the CNS.