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.
Gorelik
G
G
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina (CONICET), Buenos Aires, Argentina.
Cremaschi
G
G
Borda
E
E
Sterin-Borda
L
L
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