CONTROL BY H-2 GENES OF THE TH1 RESPONSE INDUCED AGAINST A FOREIGN ANTIGEN EXPRESSED BY ATTENUATED SALMONELLA-TYPHIMURIUM

Attenuated salmonellae represent an attractive vehicle for the deliver y of heterologous protective antigens to the immune system. Here, we h ave investigated the influence of the genetic background of the host w hich regulates the growth and elimination of Salmonella cells on the c ellular response induced against a foreign antigen delivered by an aro A Salmonella strain. We have tested CD4(+) T-cell responses (cell prol iferation and cytokine production) in various mouse strains following immunization with Salmonella typhimurium SL3261 expressing a high leve l of the recombinant Escherichia coli MalE protein. We were able to de tect a CD4(+) T-cell response against the recombinant MalE protein onl y in a restricted number of mouse strains, whereas all mice produced g ood levels of anti-MalE immunoglobulin G antibodies. The Ity gene did not play a major role in these differences in T-cell responses, since both Ity-resistant and -susceptible strains of mice were found to be u nresponsive to MalE delivered by recombinant salmonellae. In contrast, when B10 congenic mice were used, a correlation was established betwe en MalE-specific T-cell unresponsiveness and H-2 genes. The discrepanc ies described in this paper in the ability of various strains of mice to develop an efficient Th1 response against a recombinant antigen dis played by a live Salmonella vaccine underscore the difficulties that c an be encountered in the vaccination of human populations by such a st rategy.