Antigen-stimulated human interferon-gamma generation: role of accessory cells and their expressed or secreted products.

Overview

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.