Spleen cells of various mouse strains (e.g. BALB/c, C311, and CBA) reacted towards MAS (a mitogen derived from supernatants of cultured Mycoplasma arthritidis) with a marked lymphoproliferative response. This reactivity was T-cell-dependent. It was reduced by 90% after removal of macrophages by passage of the spleen cells through Sephadex G-10 columns. Addition of 2-mercaptoethanol (2-ME) to macrophage-depleted CBA spleen cells completely restored the response to MAS. Spleen cells of C57BL/6 and C57BL/10 mice were unreactive to MAS, even in the presence of macrophages, and this non-reactivity was controlled by the I-region of H-2. Other mouse strains that, similarly to C57BL/6, lack the expression of I-E on the cell surface (that is, mice of the haplotype H-2f, H-2q, and H-2s) were also non-responsive to MAS. However, the addition of 2-ME to spleen cells of non-responder mice resulted in high lymphoproliferative responses to MAS, which were as high as those of CBA spleen cells. The reaction of C57BL/6 spleen cells to MAS in the presence of 2-ME again was T-cell-dependent, as shown by data with spleen cells of homozygous nude mice and spleen cells treated by anti-thy-1 and C. A macrophage dependency of this response was also evident. When C57BL/6 spleen cells were vigorously freed of accessory cells by the use of nylon wool columns, the MAS response could no longer be restored by 2-ME.
Factor(s) in the supernatant of cultured mycoplasma arthritidis (MAS) represented potent inducers of interferon (IFN) in cultures of mouse spleen cells. Responding mouse strains included A/J, BALB/c, CBA, C3H, and DBA/2 whereas spleen cells of C57BL/6 and C57BL/10 mice were nonresponders. Interferon production was controlled by the I region of the H-2 locus. Treatment of CBA spleen cells by anti-thy-1 antibody plus C abolished IFN production. A similar effect was seen when CBA spleen cells were freed of macrophages by passage through Sephadex G-10 columns. Pure macrophages themselves, however, were not producing IFN when treated by MAS. Macrophage-depleted CBA spleen cells could be reconstituted to produce IFN by the addition of 2-ME. Interferon induction by CBA spleen cells was independent of lymphoproliferation as evidenced by experiments utilizing mitomycin C. The IFN induced by MAS represented IFN gamma (gamma), since it was acid-labile and neutralized by a specific antiserum.
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