Analysis of immunization route-related variation in the immune response to heat-killed Salmonella typhimurium in mice

Abstract

In examinations of the factors regulating the quality and quantity of the immune response to Salmonella typhimurium, we have shown previously that live and heat-killed preparations of S. typhimurium can induce gamma interferon-dominant and interleukin-4-dominant immune responses, respectively, upon intraperitoneal (i.p.) immunization of BALB/c mice. Using this system to investigate the role of the route of immunization in the immune response, we show in the present study that i.p. immunization with heat-killed S. typhimurium generates a quantitatively better immune response than does intradermal (i.d.) immunization. The quantitative differences observed between the i.p. and i.d. routes are apparent in the amount of S. typhimurium-specific antibodies produced, the extent of responses in T-cell proliferation assays, and the quantities of lymphokines generated. However, the ratios of immunoglobulin (Ig) isotypes [IgG1/IgG2a] are comparable and the relative dominance of interleukin-4 over gamma interferon is seen in both i.p.- and i.d.-immunized mice, suggesting that the predominant T-cell effector pathways triggered are not qualitatively dependent on the route of immunization. An examination of the antigenic profile recognised by the B-cell and T-cell responses in i.p.- versus i.d.-immunized mice shows that while the Western immunoblot patterns recognized by serum antibodies from the two groups of mice were not significantly different, T cells from i.p.-immunized mice recognized a broader spectrum of antigens in an immunoblot assay than did those from i.d.-immunized mice. These data suggest that there may be a significant difference in the antigen-processing ability of peritoneal and dermal antigen-presenting cells for complex antigenic formulations such as bacterial vaccines.