Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins.

摘要: Suppression of host T cell responses is one the hallmarks infection with African trypanosomes. The cellular basis for immunosuppression includes generation suppressor macrophages that down-regulate proliferative but not necessarily cytokine to both mitogen and trypanosome Ag. Since from infected animals display activation characteristics, we have asked whether products activated cells, specifically nitric oxide (NO) PG, may mediate effects observed. We demonstrate cells isolated B10.BR mice Trypanosoma brucei rhodesiense exhibited transcriptional up-regulation inducible NO synthase released significant amounts NO. levels were elevated further after stimulation mitogens or specific parasite Ag; antibody blocking experiments demonstrated this synthesis was at least partially dependent upon IFN-gamma TNF-alpha. addition substrate analogues such as NG-monomethyl-L-arginine cultures inhibited release also reversed activity displayed by cultures. PG in mice, inhibitor indomethacin had no effect on suppression when added alone However, concurrent inhibition completely blocked associated resulted recovery immunosuppression, thus revealing an epistatic between these two mediators. conclude macrophage trypanosomiasis induces reactive nitrogen intermediates which during infection.