Antigen-stimulated human interferon-gamma generation: role of accessory cells and their expressed or secreted products.
In response to cytomegalovirus (CMV) and Toxoplasma gondii antigens, T4+ cells from seropositive donors produce interferon-gamma (IFN-gamma) by different mechanisms; one (T. gondii) dependent upon and the other (CMV) largely independent of interleukin-2 (IL-2) and its receptor. To determine whether IFN-gamma-generating mechanisms unrelated to IL-2 also differ, we examined the requirement for accessory cells and their expressed or secreted products. In response to both specific antigens, IFN-gamma secretion was strictly dependent upon the presence of accessory cells (monocytes), and was largely inhibited by monoclonal antibodies to class II (HLA-DR and -DQ) but not class I MHC antigens. Both CMV and T. gondii antigens stimulated monocytes to release interleukin-1 (IL-1), and IFN-gamma production in response to both antigens was abolished by pretreatment with anti-IL-1 antibody. In contrast, the secretion of tumour necrosis factor (TNF) was not stimulated by either antigen, and IFN-gamma production was not diminished by antisera directed at TNF-alpha or TNF-beta. We conclude that CMV and T. gondii antigen-induced IFN-gamma production requires a similar accessory cell mechanism, and that soluble antigen-stimulated IFN-gamma secretion by human T4+ cells is dependent on monocytes, expression of class II MHC antigens, and the presence of IL-1.
Kelly
C D
CD
Department of Medicine, Cornell University Medical College, New York, NY.
Russo
C M
CM
Rubin
B Y
BY
Murray
H W
HW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000502:physiology*; D000953:Antigens, Protozoan / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D014122:Toxoplasma / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000956:Antigens, Viral; D006681:HLA-D Antigens; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma