Inhibition of immune reactionsin vivoby liposome associated transforming growth factor (TGF) type β1

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Abstract
In view of its potent inhibitory capacity on immune cells in culture, we wished to determine the ability of transforming growth factor (TGF) β1 to down-regulate immune responses in vivo. Preliminary experiments suggested that, at the doses used, systemic injection of soluble TGFβ1 could not affect bacterial-induced spleen enlargement in mice. Therefore, we sought to utilize a physiochemical properly of this molecule, namely its high pI, to determine possible association between the ligand and preformed liposomes possessing an opposite charge. TGFβ1 was preferentially associated with negatively charged, but not with neutral, liposomes. These TGHβ1 associated liposomes were able to deliver a suppressive signal to indicator cells in vino. Intravenous injection of TGFβ1, associated with liposomes possessing an opposite charge, into mice immunized with heat-killed Corynobacterium parvum significantly reduced the size of the spleen as well as the number of splcnocytes. Systemically administered TGFβ1 associated liposomes could also inhibit delayed type hypersensitivity reactions to Listeria monocytogenes. These data suggest that appropriately administered, TGFβ1 can inhibit immune responses in vivo.