Delayed-type hypersensitivity and immunity to Salmonella typhimurium

Abstract

Studies were carried out to correlate immunity and expression of delayed-type hypersensitivity (DTH) in mice of the C3H lineage immunized with an avirulent strain of Salmonella typhimurium (strain SL3235). This strain belongs to a class of aroA- organisms which are being considered as vaccine strains for humans and veterinary use. In a systematic study, the relationship between the mouse strain and the immunizing dose of strain SL3235 on the development of protective immunity and DTH was examined. It was found that in hypersusceptible C3H/HeJ and C3HeB/FeJ mice, several doses of strain SL3235 afforded protection against intravenous challenge doses as high as 1,300 50% lethal doses. Despite these significant levels of immunity to challenge, mice of these two strains never mounted significant DTH responses following immunization with the doses of strain SL3235 tested, which spanned 3 orders of magnitude. Nonresponsiveness was not due to antigen overload, as all of the mouse strains were comparably colonized with strain SL3235 at the time of DTH elicitation. Further, it was found that the ability of responsive C3H/HeNCrlBR mice to display DTH was dependent on the immunizing dose of strain SL3235 and that a dosage could be found that resulted in increased resistance to challenge in these mice without a concomitant display of DTH. Thus, while both induction of protective immunity and DTH were vaccine dosage dependent in the responsive mouse strain (C3H/HeNCrlBR), DTH was a less sensitive measure of protective immunity than survival. Vaccine dosages ranging over three orders of magnitude failed to yield positive footpads to the Salmonella elicitin in the nonresponsive mice. The data suggest that caution should be observed in interpreting Salmonella DTH tests that are used as screens of immune status to typhoid fever in humans, as the extent of discordance between immunity and DTH in humans is unknown.