Trypanosoma cruzi antigens down-regulate T lymphocyte proliferation by muscarinic cholinergic receptor-dependent release of PGE2.
Here we demonstrate that T. cruzi antigen molecule SAPA (shed acute phase antigen) with neuraminidase-trans sialidase activity triggers down-regulation of T lymphocyte proliferation by interacting with T lymphocyte muscarinic acetylcholine receptors (mAChR). SAPA attachment to mAChR from Lyt 2.2+ T cells resulted in synthesis of cyclic GMP (cGMP) and secretion of PGE2, an immunoregulator effector substance. These T suppressor cell signals were blunted by atropine and by indomethacin. Cell sorter analysis showed that the interaction of SAPA with purified T cells, affected the ratio of L3T4+/Lyt 2.2+ T cells increasing the percentage of Lyt 2.2+ T cells, effect that was inhibited by the mAChR antagonist, atropine. The interaction between SAPA and mAChR from Lyt 2.2+ T cells may result, therefore, in the down-regulation of the host immune response as consequence of T suppressor/cytotoxic cells activation and PGE2 release as they were observed. These results support the theory of an immunosuppressive state that contribute to the chronic course of Chagas' disease.
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Buenos Aires, Argentina.
G
G
Gorelik
G
G
Cremaschi
E
E
Borda
L
L
Sterin-Borda
D000818:Animals; D000953:Antigens, Protozoan / Q000502:physiology*; D001285:Atropine / Q000494:pharmacology; D002455:Cell Division; D014355:Chagas Disease / Q000276:immunology; D002908:Chronic Disease; D003208:Concanavalin A; D006152:Cyclic GMP / Q000276:immunology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D016861:Cyclooxygenase Inhibitors; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D003208:Concanavalin A; D001285:Atropine; D006152:Cyclic GMP; D015232:Dinoprostone; D007213:Indomethacin