DIFFERENTIAL INDUCTION OF TUMOR-NECROSIS-FACTOR-ALPHA IN MURINE AND HUMAN-LEUKOCYTES BY MYCOPLASMA ARTHRITIDIS-DERIVED SUPERANTIGEN

Mycoplasma arthritidis-derived superantigen (MAS) is exclusively produ ced by M. arthritidis, which is the only known mycoplasma to produce a superantigen. As a superantigen, MAS shows properties similar to thos e of the staphylococcal enterotoxins and related substances, such as b inding to major histocompatibility complex (MHC) class II and VP-speci fic stimulation of T cells. In this series of experiments, we demonstr ate some differences between MAS and other superantigens. MAS induced the production of tumor necrosis factor alpha (TNF-alpha) mRNA in huma n as well as in murine leukocytes. However, only in murine leukocytes was the mRNA adequately translated into the protein. In human peripher al blood mononuclear cells, we found only small amounts of TNF, wherea s in murine spleen cells ne detected levels more than three times high er. The proliferative response to MAS has been shown to be restricted to I-E alpha in the murine MHC. Furthermore, TNF was induced in I-E al pha(+) bone marrow-derived macrophages by MAS. In these cells, MAS rap idly induced very high levels of TNF and the amounts of mRNA detected correlated to the amount of protein produced. In comparison with other superantigens, including the staphylococcal enterotoxins, toxic shock syndrome toxin 1, and exfoliative toxin A, the failure of MAS to indu ce TNF-alpha in human peripheral blood mononuclear cells is specific f or MAS and not common to all superantigens. The direct activation of b one marrow-derived macrophages also seems to be specific for MAS. Thes e data suggest that the induction of TNF-alpha by MAS is dependent on the strength of binding to the MHC class II molecule.