Modification of cytotoxic T-cell response patterns by administration of hemagglutinin-specific monoclonal antibodies to mice infected with influenza A viruses.
Mice injected with any influenza A virus develop a range of virus-immune cytotoxic T lymphocytes, some of which tend to be more lytic for cells expressing the virus used for priming (subtype-specific) while others are cross-reactive for targets infected with all influenza A viruses. Treatment with large doses of either of two monoclonal antibodies (which bind to the influenza virus hemagglutinin molecule) at 3-48 h after exposure to virus tends to selectively block the generation of the more subtype-specific cytotoxic T lymphocyte subset, although the magnitude of cross-reactive effector function may also be diminished. Inhibition that is less obviously selective is also seen for a third monoclonal antibody. A reasonable explanation for these findings is that there is afferent blockage at the level of T-cell recognition of the influenza virus hemagglutinin molecule expressed on stimulator cells. The inhibitory effect of the monoclonal antibody is apparently steric. Priming with parental strain virus followed by exposure to monoclonal antibody induces a population of cytotoxic T lymphocytes which manifest decreased cytotoxic activity for target cells infected with either the parental strain virus or with a variant virus to which the monoclonal antibody does not bind. A more practical consideration is that the administration of large doses of specific immunoglobulin may interfere with the development of cell-mediated immune mechanisms. This should be considered when developing possible therapeutic protocols using monoclonal antibodies.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D006389:Hemagglutinins, Viral / Q000276:immunology*; D007114:Immunization; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006389:Hemagglutinins, Viral