Immunomodulatory activity of monophosphoryl lipid A in C3H/HeJ and C3H/HeSnJ mice.
Treatment with nontoxic monophosphoryl lipid A (MPL) derived from a polysaccharide-deficient, heptoseless Re mutant of either Salmonella typhimurium or Salmonella minnesota R595 enhanced the immunoglobulin M (IgM) anti-type III pneumococcal polysaccharide (SSS-III) antibody response of C3H/HeSnJ mice. Such an adjuvant effect was not observed in lipopolysaccharide-nonresponder C3H/HeJ mice. Nevertheless, C3H/HeJ spleen cells produced a weak mitogenic response to both preparations of MPL in vitro, and C3H/HeJ mice showed a significant increase in serum IgM levels without an increase in numbers of splenic IgM-secreting plaque-forming cells after in vivo treatment with MPL. A significant increase in serum IgG3 levels was accompanied by a transient decrease in serum IgG1 levels in C3H/HeSnJ mice given MPL; such non-antigen-specific polyclonal effects were not observed in C3H/HeJ or in athymic nu/nu mice. Since the enhanced antibody response to SSS-III has been attributed to the inactivation of suppressor T cells by MPL and since suppressor-T-cell activity is demonstrable in both C3H/HeSnJ and C3H/HeJ mice, these findings imply that (i) the suppressor T cells of C3H/HeJ mice are refractory to inactivation by MPL and (ii) some of the polyclonal and mitogenic effects produced in C3H/HeJ mice are due to the direct action of MPL on B lymphocytes.
Hiernaux
J R
JR
Ribi ImmunoChem Research, Inc., Hamilton, Montana 59840.
Stashak
P W
PW
Cantrell
J L
JL
Rudbach
J A
JA
Baker
P J
PJ
D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000917:Antibody Formation / Q000187:drug effects*; D005260:Female; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology*; D008819:Mice, Nude; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012475:Salmonella / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013296:Streptococcus pneumoniae / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D008050:Lipid A; D011135:Polysaccharides, Bacterial; C048436:monophosphoryl lipid A