The effects of Muramyldipeptide (MDP) in cell-mediated immunity

Abstract

N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) was tested in cell-mediated systems. A preparation of MDP, which yielded comparable activity to Freund's complete adjuvant in a humoral response against bovine serum albumin, was used to examine the degree of correlation between in vitro and in vivo models of cell-mediated immunity: (a) The proliferative T cell response in vitro was found to be most strongly enhanced by MDP at low antigen concentrations. The stimulation indices (SIs), however, were only enhanced at very low antigen concentrations because of a mitogenic effect of MDP in the absence of any added antigen. In vivo the proliferative response was measured in a graft-versus-host reaction where MDP caused a nonspecific (systemic) proliferation. In a host-versus-graft situation, however, MDP significantly enhanced the local proliferative response, besides causing an increased systemic ‘background’ proliferation. (b) The cytotoxic T cell response in vitro was enhanced with suboptimal and optimal antigen concentrations; with supraoptimal antigen concentrations a strong decrease in lytic activity was observed. In vivo, MDP enhanced the cytotoxic activity of peritoneal exudate cells in the same allogeneic system (H-2b anti H-2a) as the one used in vitro. This enhanced activity did not, however, enhance adoptive protection in the immunoincompetent host. (c) Cytotoxic T memory function was unaffected by MDP, both in an in vitro system using subcellular material to elicit the cytotoxic response and in vivo, when an adoptive transfer system was used to assay T memory cells for their protective capacity against tumor in the immunoincompetent host. (d) Antibody-mediated cell cytotoxicity was slightly suppressed when MDP was present in vitro; in vivo-pretreated spleen cells exhibited enhanced activity, but only at low antibody concentrations where a macrophage activity was superimposed on the K cell activity. (e) Macrophages could be activated both in vitro and in vivo to kill tumor cells effectively.