title: Deregulation of mouse antibody-forming cells in vivo in cell culture by streptococcal pyrogenic exotoxin.
abstract: An unregulated, elevated rebound of antibody levels in rabbits was shown to follow late (10 to 15 days) after steptococcal pyrogenic exotoxin (SPE)-induced immunosuppression. Because of that result we have suggested that SPE acts by preferentially inhibiting a regulatory cell which normally limits the extent of full expression of antibody formation by B-cells. We are currently testing this hypothesis in mice. NIH (Swiss Webster) mice (+/+) or NIH (Swiss Webster) mice heterozygous (+/nu) for the mutant athymic nude gene and phenotypically normal showed an elevated plaque-forming cell (PFC) response to sheep erythrocytes (SE) late (10 to 15 days) after immunosuppressive SPE treatment similar to that described in rabbits. Homozygous nude mice (nu/nu) that are phenotypically athymic normally show a reduced early (4 day) PFC response to SE (a T-cell-dependent antigen) as compared with +/nu littermates or +/+ parent strain mice. This cryptic early 4-day response was improved by injection of purified endotoxin (a B-cell mitogen), but these relatively elevated nude PFC responses had decreased to normal control (SE only)nude PFC levels before 10 days. In similar SE-injected nude mice treated instead with SPE, no elevation at 4 days was observed and, more pertinently, the late (10 to 15 day) elevated rebound of PFC levels observed in normal response controls (+/nu or +/+) was not observed. Similar experiments were subsequently conducted in Marbrook-type spleen PFC cultures during periods of 12 days. The results of these experiments paralleled the in vivo results above, and in addition showed that SPE induced a large proliferation of either +/+ or +/nu cells (T-and B-cells) in culture but had no such effect on nu/nu cells (B-cells) in culture. Purified endotoxin, the Bcell mitogen, had a better sparing effect on nu/nu cells in this respect. These results are consistent with our premise that SPE inhibits preferentially the function of a regulator of the antibody response. The regulator appears to be a T-cell and is likely a suppressor T-cell.
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D000921:Antibody-Producing Cells / Q000276:immunology*; D002452:Cell Count; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D006462:Hemolytic Plaque Technique; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012486:Salmonella typhimurium / Q000276:immunology; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013291:Streptococcus / Q000276:immunology*; D013950:Thymus Gland / Q000002:abnormalities; D014118:Toxins, Biological / Q000494:pharmacology*
chemical_list: D004731:Endotoxins; D014118:Toxins, Biological