Involvement of gamma interferon in antibody enhancement by adjuvants.
In a previous study the adjuvant action of a monophosphoryl lipid A, a nontoxic derivative of endotoxic lipopolysaccharide (LPS), was found to be negated by a monoclonal anti-gamma interferon (anti-IFN-gamma) antibody. The present investigation centered on three other adjuvants of diverse microbial origins, testing for their capacity to affect the release of IFN-gamma as an explanation for their antibody-enhancing action. The adjuvant action of each of the three, a wild-type LPS, synthetic poly(A)-poly(U) complexes, and a synthetic muramyl dipeptide, n-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester (murabutide), was transferable by adjuvant-stimulated T cells to normal spleen cells on coculture. Supernatant fluids from these T cells contained increased levels of IFN-gamma. Addition of a monoclonal anti-IFN-gamma antibody to adjuvant-stimulated spleen cell cultures reduced the adjuvant action by approximately one-half. Removal of natural killer cells from spleen cell populations prior to culture with antigen had no effect on the enhancement induced by LPS and monophosphoryl lipid A. It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal.
Odean
M J
MJ
Department of Medical Microbiology/Immunology, University of Minnesota, Duluth 55812.
Frane
C M
CM
Van derVieren
M
M
Tomai
M A
MA
Johnson
A G
AG
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011063:Poly A-U / Q000494:pharmacology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D011063:Poly A-U; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma; C033575:murabutide