Wolowczuk I, Auriault C, Gras-Masse H, Vendeville C, Balloul J M, Tartar A, Capron A
Centre d'Immunologie et de Biologie Parasitaire, Institut Pasteur, Lille, France.
J Immunol. 1989 Feb 15;142(4):1342-50.
The P28-1 Ag induces a strong protective immunity toward Schistosoma mansoni infection in various experimental models. T lymphocytes of mice immunized with the recombinant P28-1 Ag were stimulated in vitro by schistosome Ag of different development stages and by three P28-1 Ag-derived synthetic peptides. The most significant stimulation was achieved with the 24-43 peptide. The use of two fragments of this peptide showed that the P28-1 T lymphocyte specificity concerned essentially the NH2 terminal sequence of the 24-43 peptide. Moreover, T lymphocytes specific for the 24-43 peptide were stimulated by both schistosome Ag and the recombinant P28-1 protein. The passive transfer of (Th + Ts) lymphocytes recovered from P28-1 Ag-immunized mice increased the IgG response to P28-1 and its peptides during infection but did not protect against a challenge infection, such as the passive transfer of anti-P28-1 sera. In contrast, P28-1 specific Th cell lines maintained in culture for 2 mo, passively transferred a strong protection (50%) to infected mice. Supernatants of P28-1-specific T cells obtained after stimulation with the corresponding Ag, were able to confer cytotoxic properties to platelets and macrophages. The presence of IFN-gamma for the cytotoxicity mediated by platelets and macrophage activating factor for the cytotoxicity mediated by macrophages in these supernatants is in a large part responsible for the parasite killing observed. Finally, a preliminary immunogenetic approach with H-2 congenic mice on BALB background showed that the P28-1 Ag T cell response was under the control of the MHC and that the H-2b haplotype determined a low response to P28-1 Ag and its peptides while H-2d and k haplotypes determined high responders.
P28 - 1抗原在各种实验模型中可诱导针对曼氏血吸虫感染的强大保护性免疫。用重组P28 - 1抗原免疫的小鼠T淋巴细胞,在体外受到不同发育阶段的血吸虫抗原和三种P28 - 1抗原衍生的合成肽的刺激。用24 - 43肽获得了最显著的刺激效果。使用该肽的两个片段表明,P28 - 1 T淋巴细胞特异性主要涉及24 - 43肽的NH2末端序列。此外,24 - 43肽特异性的T淋巴细胞受到血吸虫抗原和重组P28 - 1蛋白的刺激。从P28 - 1抗原免疫的小鼠中回收的(Th + Ts)淋巴细胞的被动转移,在感染期间增加了对P28 - 1及其肽的IgG反应,但不能预防攻击感染,如抗P28 - 1血清的被动转移。相反,在培养中维持2个月的P28 - 1特异性Th细胞系,可将强大的保护作用(50%)被动转移给感染小鼠。用相应抗原刺激后获得的P28 - 1特异性T细胞的上清液,能够赋予血小板和巨噬细胞细胞毒性特性。这些上清液中血小板介导的细胞毒性所需的IFN - γ以及巨噬细胞介导的细胞毒性所需的巨噬细胞活化因子的存在,在很大程度上导致了观察到的寄生虫杀伤。最后,在BALB背景上用H - 2同源基因小鼠进行的初步免疫遗传学研究表明P28 - 1抗原T细胞反应受MHC控制,并且H - 2b单倍型对P28 - 1抗原及其肽的反应较低,而H - 2d和k单倍型决定了高反应性。