EXPRESSION OF HEAT SHOCK PROTEIN WHICH CONTROLS THE INFECTIVITY OF TOXOPLASMA AND HOST RESISTANCE AGAINST INFECTION

在其他宿主和微生物系统中的热休克蛋白的效应和调节功能的特性应该提供洞察机制的毒力和保护性适应，控制毒力。因此，似乎热休克蛋白可以承担在许多宿主-寄生虫的关系，包括宿主的抗性，否则破坏性的有毒寄生虫至关重要。无论如何，我们的一系列实验表明，HSP 65在腹腔巨噬细胞上的表达与抑制弓形虫低毒力株和高毒力株感染的破坏性后果的能力密切相关，从这些基础上，HSP 65的表达机制和生物学作用可能如下。作为低毒力弓形虫感染后的第一步，循环γ δ T细胞识别弓形虫来源的HSP 65或宿主来源的HSP 65，然后它们积累并活化。在第二步，巨噬细胞被γ δ激活， ...更多信息 T细胞可能通过某些细胞因子途径表现出增强的呼吸爆发释放有害分子，例如氧代谢产物，这是对抗细胞内病原体如刚地弓形虫的主要保护机制。作为第三步，活化的巨噬细胞合成内源性HSP 65以保护自身免受这些毒性分子的攻击，修复自身受损的功能或有效地呈递抗原。最后，对HSP 65反应的γ δ T细胞和α T细胞或对弓形虫抗原特异的α T细胞进一步积累并被激活。这些T细胞直接破坏宿主巨噬细胞或激活巨噬细胞以杀死细胞内的弓形虫寄生虫。我们在这里发现，γ δ T细胞而不是α T细胞参与诱导已获得抗弓形虫病的宿主巨噬细胞上的HSP 65。然而，HSP 65的表达机制以及该蛋白在抗感染中的作用仍不清楚。此外，阐明诱导HSP 65表达的γ δ T细胞和积累识别HSP 65的γ δ T细胞是否涉及相同的功能亚群，以及γ δ T细胞的前一个和后一个亚群是否识别彼此不同的抗原或HSP 65的相同表位是非常重要的。此外，研究γ δ T细胞和α T细胞在保护性免疫中的关系是有意义的，两者都具有诱导这种蛋白的能力。少

Characterization of effector and regulatory functions of HSPs in other hosts and microbial systems should provide insight into mechanisms of virulence and protective adaptations that control virulence. Thus, it seems likely that HSPs could assume a critical importance in numerous host-parasite relationships, including resistance of host to otherwise destructively virulent parasites. At any rate, it seems clear from a series of our experiments that expression of HSP65 on peritoneal macrophages correlates dramatically with capacity to inhibit destructivc consequences of infection with both low-virulence and high-virulence strains of T.gondii.From these bases, the expression mechanism and the biological role of HSP65 may be as follows. As first step after infection with a low-virulence of Toxoplasma, circulating gammadelta T cells recognize either Toxoplasma-derived HSP65 or host-derived HSP65, and then they accumulate and activated. At the second step, macrophages activated by gammadelta … More T cells probably via certain cytokine pathways exhibit enhanced respiratory burst releasing noxious molecules, e.g.oxygen metabolites, a major protective mechanism against intracellular pathogens like T.gondii. As the third stcp, activated macrophages synthesize endogenous HSP65 for protection against these toxic molecules, for repairment of damaged functions of themselves or for effective antigen-presentation. Finaly, either gammadelta T cells and alphabeta T cells reactive to HSP65 or alphabeta T cells specific for Toxoplasma antigen further accumulate and are activated. Such T cells directly destroy the host macrophages or activate macrophages to kill the intracellular Toxoplasma parasites.We showed here that gammadelta T cells rather than alphabeta T cells participate in the induction of HSP65 on macrophages of hosts which have acquired resistance against toxoplasmosis. However, it stili remains undetermined about the mechanisms of expression of HSP65 and the role of this protein in the protection against this infection. Furthermore, it is very important to elucidate whether gammadelta T cells which induce the expression of HSP65 and those which accumulate recognizing HSP65 involve in the same functional subset, and whether the former and the latter subset (s) of gammadelta T cells recognize different antigens each other or the same epitope of HSP65. Moreover, it is of interest to investigate the relationship between gammadelta T cells and alphabeta T cells in protective immunity, both of which have an ability to induce this protein. Less