ネズミチフス症における免疫成立機序に関する研究

Abstract

Two outbred mouse strains, ddY and CF1, were tested for their ability to be protected against infection with Salmonella typhimurium by several types of salmonella vaccines. These strains have the same levels of innate susceptibility to S. typhimurium, and also have the same capacity to develop delayed-type hypersensitivity (DTH) to salmonella antigens. Both the crude ribosomal fraction (CRF) and live-cell vaccines conferred acquired resistance on both strains, characterized by greater responses of T cells to salmonella antigens. Mice of the ddY strain were also protected by the purified transfer RNA (tRNA) vaccine, which was free of O antigens, but CF1 mice were not, despite the presence of T-cell reactivity with salmonella antigens. Neither strain was protected by phenol-water-extracted lipopolysaccharide (LPS). The tRNA-immunized CF1 mice were protected by transfer of antiserum to CRF, but not by transfer of anti-LPS antibody. This antiserum to CRF, however, did not transfer acquired resistance into non-immune mice of either strain. These observations suggest that CF1 mice may require an antibody to another non-O antigen existing in CRF to develop acquired resistance, and that stimulation of the defense system by tRNA may be essential to the development of acquired resistance in CF1 mice. The active component in CRF of Salmonella typhimurium, capable of inducing protective antibody, was partially purified by two series of chromatography (Sephadex G-150 and DEAE-Sepharose CL 6B) after sodium dodecyl sulphate (SDS)-treated CRF was precipitated with ammonium sulphate. The major active component was eluted by 0.4-0.45 M Nacl from DEAE-Sepharose CL 6B, and its molecular weight was 43,000 as determined by SDS-polyacrylamide gel electrophoresis. Immunization with the fraction containing 43,000 component alone did not always confer protection on CF1 mice, but its administration together with either the purified tRNA or Freund's complate adjuvant (FCS) was much more effective against infection with S. typhimurium. Western blot analysis showed that 43,000 component did not react to ansiserum to LPS, but to antiserum to CRF. The antibody elicited by non-O antigenic component and the cell-mediated resistance stimulated by the adjuvant effect of RNA together confer effective protection on CF1 mice.