TOXOPLASMA-GONDII INFECTION INDUCES SPECIFIC NONRESPONSIVENESS IN LYMPHOCYTES BEARING THE V-BETA-5 CHAIN OF THE MOUSE T-CELL RECEPTOR

We recently reported a superantigen activity associated with Toxoplasm a gondii tachyzoites that in vitro induces preferential expansion of V beta 5(+) T lymphocytes following parasite stimulation of nonimmune c ells. In the experiments presented in this work, V beta 5(+) lymphocyt e function was examined ex vivo using mice undergoing chronic and acut e infection with the avirulent parasite strain ME49 or acutely infecte d with the attenuated mutant ts-4, Cells bearing the TCR V beta 5 chai n were found to be increased by 1.5- to twofold during acute infection , whereas during the chronic phase, modest decreases (similar to 20%) in cells of the latter subset were observed. When splenocytes from chr onically infected animals were stimulated in vitro with tachyzoites, t he preferential expansion of V beta 5(+) lymphocytes seen using cells from normal mice was not observed. Furthermore, when purified T lympho cytes were cultured with plate-bound V beta 5-specific mAb, we found t hat in contrast to normal and acutely infected animals, cells from chr onically infected and ts-4-vaccinated mice were nonresponsive to TCR-i nduced stimulation (70 to 90% reduction relative to normal cells). In control experiments, mAb to CD3 and V beta 8 elicited normal responses in the same animals. Similarly, in contrast to normal splenocytes, ce lls from chronically infected mice failed to produce IFN-gamma in resp onse to anti-V beta 5 mAb. These data indicate that V beta 5(+) tells are rendered nonresponsive as a result of in vivo encounter with T. go ndii, and as such they provide the first demonstration of V beta-speci fic anergy induced by a protozoan parasite.