IMMUNIZATION OF HL4-B27 TRANSGENIC AND NON TRANSGENIC MICE WITH SALMONELLA-TYPHIMURIUM RESULTS PREDOMINANTLY IN THE GENERATION OF PROLIFERATIVE T-CELL RESPONSES
Jh. Ringrose et al., IMMUNIZATION OF HL4-B27 TRANSGENIC AND NON TRANSGENIC MICE WITH SALMONELLA-TYPHIMURIUM RESULTS PREDOMINANTLY IN THE GENERATION OF PROLIFERATIVE T-CELL RESPONSES, Clinical rheumatology, 15, 1996, pp. 79-85
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.