The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice.
Parameters of the virus-specific T-cell response were analysed in order to dissect the contribution of CD4+ and CD8+ T cells to cell-mediated immunity to lymphocytic choriomeningitis virus. In MHC class II deficient mice, initial T-cell responsiveness was not impaired, but virus clearance was delayed, and virus-specific Td activity declined more rapidly. Furthermore, class I restricted Tc memory appeared to be impaired in these mice. To directly evaluate the role of CD4+ cells in virus clearance and T-cell mediated inflammation, MHC class I deficient mice were also studied. No virus-specific delayed-type hypersensitivity reaction was detected following infection of the footpad, and only a few mice died from intracerebral challenge. However analysis of markers of T-cell activation as well as direct evaluation of CSF inflammation unveiled a low degree of T-cell activation and a chronic cellular exudate. This low-grade response was associated with some degree of virus control as organ titres were lower in these animals than in matched T-cell deficient nu/nu mice or class I deficient mice treated with anti-CD4 monoclonal antibody. This confirms that CD4+ cells are not needed to induce a virus-specific CD8+ T-cell response, but our findings strongly suggest that CD4+ T cells are critical for maintaining full antiviral immunity. Furthermore, CD4+ T cells per se have a low potential for mediating virus-specific inflammation that is associated with a low degree of virus control.
Christensen
J P
JP
Institute of Medical Microbiology and Immunology, University of Copenhagen, Panum Institute, Denmark.
Marker
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Thomsen
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D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013154:Spleen / Q000166:cytology / Q000821:virology; D001613:beta 2-Microglobulin / Q000172:deficiency
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin