Modified immunological status of anti-IL-10 treated mice.
We have shown that continuous treatment of mice from birth to adulthood with neutralizing anti-IL-10 antibodies leads to specific depletion of Ly1 B cells, while conventional B cells remain normal in terms of number, phenotype, and function. Extending our characterization of these animals, we show here that anti-IL-10 treated mice can be distinguished from untreated or isotype control treated mice by several other criteria. Anti-IL-10 treated mice contained substantially elevated levels of circulating TNF-alpha, and in many cases circulating IL-6, and were profoundly susceptible to death by LPS-induced shock, a monokine mediated inflammatory reaction. Analysis of serum immunoglobulin levels in anti-IL-10 treated mice revealed a decrease in serum IgA levels to accompany the previously reported reduction in serum IgM, plus a striking increase in IgG2a and IgG2b levels. Further investigation of the Ly1 B cell depletion of anti-IL-10 treated mice revealed that this effect was transient as evidenced by the return of Ly1 B cells in normal numbers 8 weeks after anti-IL-10 treatment was discontinued. The Ly1 B cell depletion that occurred during anti-IL-10 treatment was found to be compensated by an increase in peritoneal T cells and granulocytes. Finally, while anti-IL-10 treated mice were unable to produce antibodies to phosphorylcholine and alpha 1,3-dextran, they developed normal antibody responses following intraperitoneal injections of TNP-Ficoll, suggesting the existence of subcategories within the family of thymus independent type II polysaccharide antigens. These data are discussed within the context of their implications for the roles of IL-10 and Ly1 B cells in the immune system.
Ishida
H
H
DNAX Research Institute, Palo Alto 94304.
Hastings
R
R
Thompson-Snipes
L
L
Howard
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology; D007136:Immunoglobulins / Q000097:blood*; D016753:Interleukin-10 / Q000502:physiology*; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000955:Antigens, T-Independent; D016207:Cytokines; D007136:Immunoglobulins; D016753:Interleukin-10