A study of the cellular and molecular mediators of the adjuvant action of a nontoxic monophosphoryl lipid A

Abstract

A detoxified endotoxin, termed monophosphoryl lipid A (MPL, Ribi), has been shown to increase antibody forming cell numbers in aging Balb mice both in vivo and in vitro. Separation of splenocytes from aging mice into purified T, B and adherent cell populations and subsequent incubation of each with MPL and admixture with their cellular counterparts and antigen, revealed only the T cell compartment capable of transferring the adjuvant action. Incubation of purified T cells from aging mice with MPL for 2 hr, followed by washing and culture for 48 hr, resulted in a supernatant fluid which enhanced antibody formation in cultures of aging spleen cells. This enhancing action was eliminated by an antiserum containing anti-alpha/beta-gamma interferon, but not by an anti-alpha/beta interferon antiserum. These data, as well as evidence gained by others as discussed, suggests the hypothesis wherein MPL increases antibody formation in aging mice by inducing the helper T cell population to secrete interferon gamma. The latter activates the macrophage to secrete increased levels of interleukin 1, thereby resulting in increased responsiveness throughout the ensuing sequence of cellular and molecular events leading to antibody synthesis.