The role of CD4+ T cells in cell-mediated immunity to LCMV: studies in MHC class I and class II deficient mice

Scand J Immunol. 1994 Oct;40(4):373-82. doi: 10.1111/j.1365-3083.1994.tb03477.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Susceptibility / immunology
  • Female
  • Histocompatibility Antigens Class I / physiology
  • Histocompatibility Antigens Class II / physiology
  • Hypersensitivity, Delayed / immunology
  • Immunity, Cellular
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Spleen / cytology
  • Spleen / virology
  • beta 2-Microglobulin / deficiency

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • beta 2-Microglobulin