Immunization of HLA-B27 transgenic and non transgenic mice with Salmonella typhimurium results predominantly in the generation of proliferative T cell responses.

ABSTRACT

Reactive arthritis (ReA) due to Gram-negative intestinal bacteria or Chlamydia, is associated by an unknown mechanism with HLA-B27. Like other MHC class I molecules, HLA-B27 presents antigenic peptides derived from intracellular proteins to CD8+ cytotoxic T cells (CTL). In humans however, CTL specific for ReA associated bacteria have been reported in a limited number of studies. This may be caused by an inefficient in vivo induction of CTL against such micro-organisms. In the present study we addressed the question whether and to what extend mice transgenic for HLA-B27 are able to generate CTL against Salmonella typhimurium after immunization. To this end both HLA-B27 transgenic and non transgenic mice were immunized i.p., i.v. or orally, receiving a secondary challenge four weeks later. One day after infection with Salmonella, bacteria could be cultured from spleen and liver. There was no significant difference in the number of bacteria cultured from these organs between both groups of mice. Spleen cells from all immunized mice proliferated specifically in the presence of heat killed Salmonella but not in the presence of heat killed Yersinia. No proliferation of spleen cells from naive mice was observed in the presence of heat killed Salmonella, excluding the possibility that Salmonella antigens were mitogenic. Only in one out of 6 mice immunized i.v. with Salmonella Salmonella specific CTL could be generated. In order to rule out the possibility that in HLA-B27 transgenic mice the HLA-B27 molecule is not used as a restriction element by murine T cells, CTL were raised against the male minor histocompatibility (mH) antigen H-Y. Both murine class I as well as HLA-B27 restricted CTL could be generated. In conclusion this study demonstrates that MHC class I restricted CTL specific for the Gram-negative bacterium Salmonella typhimurium are difficult to generate in contrast to proliferative responses which can be easily demonstrated. This may comparable in humans where in the majority of studies bacteria specific T cells isolated from ReA patients appear to be CD4+ and class II restricted.