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 Toxoplasma gondii tachyzoites that in vitro induces preferential expansion of V beta 5+ T lymphocytes following parasite stimulation of nonimmune cells. In the experiments presented in this work, V beta 5+ lymphocyte function was examined ex vivo using mice undergoing chronic and acute infection with the avirulent parasite strain ME49 or acutely infected with the attenuated mutant ts-4. Cells bearing the TCR V beta 5 chain were found to be increased by 1.5- to twofold during acute infection, whereas during the chronic phase, modest decreases (approximately 20%) in cells of the latter subset were observed. When splenocytes from chronically infected animals were stimulated in vitro with tachyzoites, the preferential expansion of V beta 5+ lymphocytes seen using cells from normal mice was not observed. Furthermore, when purified T lymphocytes were cultured with plate-bound V beta 5-specific mAb, we found that in contrast to normal and acutely infected animals, cells from chronically infected and ts-4-vaccinated mice were nonresponsive to TCR-induced 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, cells from chronically infected mice failed to produce IFN-gamma in response to anti-V beta 5 mAb. These data indicate that V beta 5+ cells are rendered nonresponsive as a result of in vivo encounter with T. gondii, and as such they provide the first demonstration of V beta-specific anergy induced by a protozoan parasite.
Denkers
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EY
Immunobiology Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Caspar
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P
Hieny
S
S
Sher
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D002908:Chronic Disease; D017635:Clonal Anergy; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D016052:Protozoan Vaccines / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000469:parasitology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016052:Protozoan Vaccines; D016693:Receptors, Antigen, T-Cell, alpha-beta