Unexpected induction of unresponsiveness by vaccination with transformed Salmonella typhimurium.

Rats vaccinated with attenuated Salmonella typhimurium transformed with a vector containing the v2 exon of CD44 (SL-v2) were not protected and developed thymic metastases at a high rate. This was surprising because there was evidence for concomitant induction of a CD44v2-specific helper and cytotoxic T-cell response. The inefficacy of vaccination was partly caused by tumor escape and tumor-induced immunosuppression. More important were the facts that (i) BSpl2v2 cells migrated from the intraperitoneal implantation site to the thymus and (ii) after vaccination with transformed attenuated Salmonella typhimurium, a small number of dendritic cells, which had transcribed the cDNA insert, were detected in the thymus. In the thymic environment, these v2 presenting dendritic cells, as well as the BSp12v2 tumor cells, supported tolerance induction. Thus, vaccination with tumor-associated differentiation antigens, which in many instances have induced antitumor response, may deteriorate survival time and rate if vaccination is accompanied by presentation of the antigen during intrathymic T-cell selection.