Impaired generation of anti-viral cytotoxicity against lymphocytic choriomeningitis and vaccinia virus in mice treated with CD4-specific monoclonal antibody.
The role of CD4+ helper T cells in induction of anti-viral cytotoxic T-cell response was investigated by treating normal and thymectomized C57B1/6 mice with CD4-specific monoclonal antibodies (MoAb). In CD4-specific MoAb-treated mice infected with Vaccinia or lymphocytic choriomeningitis virus (LCMV), cytotoxic T-cell activity was 5-15 times lower than in normal controls when measured in a 51Cr release assay and computed as lytic units 6 and 8 days respectively after virus inoculation. This difference in the levels of effector T-cell activities did not reflect slower kinetics of cytotoxic T-cell induction in antibody-treated versus control mice, since it was also obvious at 8 days after infection for Vaccinia virus and 10 and 12 days after inoculation with LCMV. CD4-specific MoAb-induced inhibition of cytotoxic T-cell responses in vivo was seen up to 150 days after treatment in thymectomized mice. However, no significant suppressive effect of the same antibody treatment on T-cell cytotoxicity could be observed in animals treated on day 3 or later after infection with Vaccinia virus. Injection of CD4-depleted mice with recombinant interleukin 2 (rIL-2) partially corrected the impaired virus-specific cytotoxic T-cell response, suggesting that IL-2 supply may be limiting in mice lacking T helper cells.
Leist
T P
TP
Institute for Pathology, University Hospital, Zurich, Switzerland.
Kohler
M
M
Zinkernagel
R M
RM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013934:Thymectomy; D013997:Time Factors; D014616:Vaccinia virus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007376:Interleukin-2