The use of inbred and congenic mouse strains established that toxicity and death induced by Mycoplasma arthritidis associates with the haplotype expressed at the murine major histocompatibility complex. Mice bearing H-2k and H-2d are susceptible, whereas those bearing H-2b are much more resistant. Mice susceptible to toxicity exhibited massive peritoneal adhesions and a decreased ability to clear organisms from the peripheral circulation. However, the severity of acute arthritis developing over a 3-month period was not statistically related to the haplotype expressed at the major histocompatibility complex. Lymphocyte activation in vitro by a soluble T-cell mitogen is also dependent on a similar haplotype expression.

No abstract

Cell-free supernatants from cultures of Mycoplasma arthritidis induced significant levels of interferon when cocultured with murine splenic cells. On the basis of physicochemical characteristics and antibody neutralization studies, the antiviral substance was identified as gamma interferon. Use of inbred and congenic mouse strains established that splenic cells from mice expressing the H2k and H2d haplotypes produced interferon in response to M. arthritidis culture supernatants, but those from mice with H2b and H2q haplotypes did not. Further studies with recombinant mouse strains established that interferon induction by the mycoplasma supernatant was associated with the haplotype expressed at the I-E/I-C subregion of the murine major histocompatibility complex. The specificity seen for interferon induction was identical with that reported earlier for induction of cytotoxic lymphocytes and for lymphocyte proliferation in response to the mitogen. All of these reactions appear to be dependent upon binding of the mitogen to specific I-E/I-C region-coded products present on splenic cell surfaces. The observations presented introduce the concept that microbial mitogens or their lymphokine products might modify immune responses and defense mechanisms of the naive host in a genetically restricted manner.

No abstract

The peripheral blood lymphocytes from eight healthy volunteers produced significant amounts of interferon (IFN) when co-cultured with a recently discovered mitogen preparation derived from cultures of Mycoplasma arthritidis (MAS). Maximum levels of 281 to 2187 U were reached after 3 to 4 days of incubation. The IFN was characterized as IFN gamma on the basis of pH and heat lability, and neutralization with anti-human IFN gamma but not anti-IFN alpha. A monoclonal antibody to HLA.DR determinants suppressed IFN induction and lymphocyte proliferation when co-cultured with MAS but was not effective against PHA-induced IFN and proliferation; PHA-induced proliferation was enhanced in the presence of the antibody. Anti-HLA.DR-mediated inhibition of lymphocyte functions, however, was not specific for MAS inasmuch as viral-induced IFN was also suppressed, as was Con A-induced proliferation. These and other studies suggest that the cellular requirement for T cell activation by MAS, PHA, and Con A may all be distinct.