NONSPECIFIC MODULATION OF THE IMMUNE-RESPONSE WITH LIPOSOMAL MENINGOCOCCAL LIPOPOLYSACCHARIDE - ROLE OF DIFFERENT CELLS AND CYTOKINES

The immunomodulating action of Neisseria meningitidis lipopolysacchari de (LPS) incorporated into liposomes and the activation of different p opulations of immunocompetent cells or the secretion of cytokines were studied. LPS stimulated an anti-sheep red blood cell (SRBC) plaque-fo rming cell response in the spleen of mice after simultaneous injection of LPS and SRBC bur if LPS was administered 3 days before the immuniz ation with SRBC the response to SRBC was strongly suppressed. After th e incorporation of LPS into liposomes the stimulation index was increa sed from 6 to 19 and the liposomal LPS did not suppress the immune res ponse to SRBC. The incorporation of LPS into liposomes leads to enhanc ement of B-mitogenic properties of LPS, as liposomal LPS stimulated th e proliferation of splenocytes in mice better than free LPS and has no influence on the thymocytes. The liposomal LPS induced more prolonged and significant accumulation of IgM-secreting cells in the spleen of mice in comparison with the free LPS. Liposomal LPS also induced more active accumulation of lFN-gamma in human peripheral blood mononuclear cells and less active accumulation of monokines, contributing to the realization of the toxic properties of endotoxin (IL-1 alpha, TNF-alph a, IL-6 and GM-CSF). These results demonstrated that the incorporation of N. meningitidis LPS into liposomes dramatically changed its immuno modulating activity. The data obtained are important for the construct ion of an adjuvant formulation for synthetic immunogens capable of ind ucing genetically unrestricted immune responses.