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 T-d activity declined more rapidly. Furthermore, class I restricted T-c 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.