INVOLVEMENT OF T-CELLS IN ENHANCED RESISTANCE TO KLEBSIELLA-PNEUMONIAE SEPTICEMIA IN MICE TREATED WITH LIPOSOME-ENCAPSULATED MURAMYL TRIPEPTIDE PHOSPHATIDYLETHANOLAMINE OR GAMMA-INTERFERON

We have previously shown that prophylactic administration of the lipos ome-encapsulated immunomodulating agents muramyl tripeptide phosphatid ylethanolamine (MTPPE) and gamma interferon (IFN-gamma) results in str ongly increased survival of mice from a normally lethal septicemia wit h Klebsiella pneumoniae. It was anticipated that the treatment acts on macrophages and nonspecifically augments host resistance to various i nfections. In the present study, we provide evidence for a keg role fo r T cells in host defense potentiation by the liposomal immunomodulato rs toward K, pneumoniae septicemia. It is shown that both CD4 and CDS cells are important in immunomodulation, most likely due to production of IFN-gamma, Depletion of circulating IFN-gamma resulted in strong r eduction of the antimicrobial host defense activation, Administration of interleukin-10 resulted in decreased antimicrobial host defense act ivation by liposomal immunomodulators. Moreover, administration of lip osomal immunomodulators was shown to induce predominantly T-helper typ e 1 (Th1) cell populations in the spleen. These findings indicate that immunomodulation with liposomal MTPPE and IFN-gamma, favors Th1 and N K cell activation.