Priming for in vitro and in vivo anti-human T lymphotropic virus type 1 cellular immunity by virus-related protein reconstituted into liposome

In vitro and in vivo anti-human T lymphotropic virus type 1 (HTLV-1) cellular immunity was examined by immunizing rats with a truncated hybrid protein (228 amino acids) of gag and env of HTLV-1 produced by Escherichia coli. Animals were immunized with the hybrid protein reconstituted into mannan-derivative-coated liposomes (gag-env-lipo). In vitro sensitization with a HTLV-1-positive cell line, TARS-1, of spleen cells obtained from these animals generated killer cells specific for syngeneic HTLV-1-positive cells. No killer activity was generated when spleen cells were obtained from animals immunized with the hybrid protein alone, the liposome alone, or the hybrid protein reconstituted into conventional liposomes with no polysaccharide coating. Killer cells were CD8⁺ CTL restricted to MHC class I. Analysis of CD8⁺ and CD4⁺ subsets in spleens showed the existence of primed CD8⁺ T cells in animals immunized with gag-env-lipo. Rats immunized with gag-env-lipo displayed accelerated rejection of TARS-1 but not of two other HTLV-1-negative tumor lines. Injection of carrageenan into animals strongly inhibited generation of killer cells, which indicates the necessity of macrophages for priming of CD8⁺ T cells with gag-env-lipo. Injection of carrageenan also cancelled in vivo immunity against HTLV-1⁺ cells induced with gag-env-lipo. These results, taken together, indicate that exogenous protein reconstituted into appropriate liposomes can effectively prime MHC class I restricted CD8⁺ T cells in vivo with macrophage dependency.