Protective effect of a T-cell-dependent immunosuppressive, B-cell-mitogenic protein (F3'EP-Si, or P90) produced by Streptococcus intermedius.
The role of a previously described bacterial protein (F3'EP-Si), now designated P90, in the survival of Streptococcus intermedius in the host was investigated, and the immunosuppressive and B-cell-mitogenic effects of this protein were further characterized. C57BL6 mice treated with P90 were about 50 times more susceptible to infection with this bacterium than untreated mice. One of seven splenocytes of C57BL/6 mice were activated by P90. Marked splenomegaly was observed in mice treated with P90, with increased numbers of splenic mononuclear cells and polyclonal immunoglobulin-secreting plaque-forming cells. Peak responses were seen on day 3 for immunoglobulin M (IgM) and on day 5 for IgG, with an isotypic pattern consisting predominantly of IgG2a and IgG2b. When mice were treated with P90 before being primed with sheep erythrocytes, polyclonal immunoglobulin synthesis was accompanied by an ephemeral stimulation of the specific immune response against sheep erythrocytes that was quickly replaced by a dramatic immunosuppression. In contrast, when mice were treated with P90 after being primed, the polyclonal activation was comparatively much less evident and there was no suppression of the specific immune response. Immunosuppression was considerably reduced in mice thymectomized as adults or depleted of CD8+ cells. Adoptive transfer experiments showed that B cells obtained from P90-treated mice were less able to respond to an antigenic challenge, even in the presence of normal T cells, and that T cells obtained from P90-treated mice could actively suppress the specific immune response of normal B cells.
Lima
M
M
Department of Immunology, Institute for Biomedical Sciences Abel Salazar, Porto, Portugal.
Bandeira
A
A
Portnoi
D
D
Ribeiro
A
A
Chaves
M A
MA
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D001426:Bacterial Proteins / Q000494:pharmacology*; D016827:CD8 Antigens / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D013291:Streptococcus / Q000378:metabolism*; D013601:T-Lymphocytes / Q000502:physiology*
D001426:Bacterial Proteins; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D008934:Mitogens