IMMUNIZATION OF HL4-B27 TRANSGENIC AND NON TRANSGENIC MICE WITH SALMONELLA-TYPHIMURIUM RESULTS PREDOMINANTLY IN THE GENERATION OF PROLIFERATIVE T-CELL RESPONSES

Reactive arthritis (ReA) due to Gram-negative intestinal bacteria or C hlamydia, is associated by an unknown mechanism with HLA-B27. Like oth er MHC class I molecules, HLA-B27 presents antigenic peptides derived from intracellular proteins to CD8(+) cytotoxic T cells (CTL). In huma ns however, CTL specific for ReA associated bacteria have been reporte d 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 trans genic for HLA-B27 are able to generate CTL against Salmonella typhimur ium after immunization. To this end both HLA-B27 transgenic and non tr ansgenic mice were immunized i.p., i.v. or orally, receiving a seconda ry challenge four weeks later. One day after infection with Salmonella , bacteria could be cultured from spleen and liver. There was no signi ficant difference in the number of bacteria cultured from these organs between both groups of mice. Spleen cells from all immunized mice pro liferated specifically in the presence of heat killed Salmonella but n ot in the presence of heat killed Yersinia. No proliferation of spleen cells from naive mice,vas observed in the presence of heat killed Sal monella, excluding the possibility that Salmonella antigens were mitog enic. Only in one out of 6 mice immunized i.v. with Salmonella Salmone lla specific CTL could be generated, In order to rule out the possibil ity that in HLA-B27 transgenic mice the HLA-B27 molecule is not used a s a restriction element by murine T cells, CTL were raised against the male minor histocompatibility (mil) antigen H-Y. Both murine class I as well as HLA-B27 restricted CTL could be generated. In conclusion th is study demonstrates that MHC class I restricted CTL specific for the Gram-negative bacterium Salmonella typhimurium are difficult to gener ate in contrast to proliferative responses which can be easily demonst rated. 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.