Inactivation of suppressor T-cell activity by nontoxic monophosphoryl lipid A.
Treatment with nontoxic monophosphoryl lipid A (MPL), which was derived from a polysaccharide-deficient, heptoseless Re mutant of Salmonella typhimurium, was found to inactivate suppressor T-cell activity, as evidenced by a decrease in the degree of low-dose immunological paralysis expressed and an increase in the magnitude of the antibody response to type III pneumococcal polysaccharide. The effects produced, which could not be attributed to the polyclonal activation of immune B cells by MPL, were dependent upon the dose of MPL used, as well as the time when MPL was given relative to low-dose priming or immunization with type III pneumococcal polysaccharide. Neither amplifier nor helper T-cell activity was decreased by treatment with the same, or larger, doses of MPL. The significance of these findings to the use of MPL as an immunological adjuvant or an immunomodulating agent is discussed.
Baker
P J
PJ
Laboratory of Microbial Immunity, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Hiernaux
J R
JR
Fauntleroy
M B
MB
Prescott
B
B
Cantrell
J L
JL
Rudbach
J A
JA
D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D007108:Immune Tolerance / Q000187:drug effects*; D007115:Immunization Schedule; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae; D013329:Structure-Activity Relationship; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D008050:Lipid A; D011135:Polysaccharides, Bacterial; C048436:monophosphoryl lipid A