Böhm W, Schirmbeck R, Elbe A, Melber K, Diminky D, Kraal G, van Rooijen N, Barenholz Y, Reimann J
Institute for Medical Microbiology, University of Ulm, Germany.
J Immunol. 1995 Oct 1;155(7):3313-21.
Injection of low doses of particulate hepatitis B surface Ag (HBsAg) into H-2d mice without adjuvants primes an Ld-restricted, S28-39-specific T cell response. This study indicates that dendritic cells (DC) and macrophages (M phi) both serve as APCs that support priming of CD8+ CTL precursors in vivo to exogenous HBsAg particles. After transfer into a syngeneic, naive host, HBsAg particle-pulsed DC, either freshly purified from skin or derived from a cloned DC line, efficiently primed class I-restricted, HBsAg-specific CTL precursors. M phi, either harvested from the peritoneal cavity or generated in macrophage-CSF-stimulated bone marrow cell cultures in vitro or derived from established, cloned M phi lines (PU5-1.8, J774A.1), pulsed with HBsAg particles in vivo or in vitro, elicited a class I-restricted, HBsAg-specific CTL response after adoptive transfer into naive hosts. The class I-restricted CTL response induced by HBsAg particle immunization was suppressed in carrageenan-treated mice, but was restored when carrageenan-treated mice were immunized with syngeneic, HBsAg-pulsed M phi. Selective elimination of M phi by liposome-incorporated dichloromethylene-diphosphonat did not suppress the induction of a CTL response of H-2d mice by HBsAg particle immunization. HBsAg-pulsed, freshly prepared DC are more potent than pulsed M phi in priming class I-restricted CTL in vivo. The relative importance of both types of APC in priming CTL remains to be resolved.
在无佐剂情况下,向H-2d小鼠注射低剂量颗粒状乙型肝炎表面抗原(HBsAg)可引发Ld限制的、S28 - 39特异性T细胞反应。本研究表明,树突状细胞(DC)和巨噬细胞(M phi)均作为抗原呈递细胞(APC),在体内支持外源性HBsAg颗粒对CD8 + CTL前体的致敏。将HBsAg颗粒脉冲处理的DC(无论是从皮肤新鲜纯化的还是源自克隆DC系)转移到同基因的未致敏宿主后,能有效地引发I类限制的、HBsAg特异性CTL前体。从腹腔收获的M phi,或在体外巨噬细胞集落刺激因子刺激的骨髓细胞培养物中产生的M phi,或源自已建立的克隆M phi系(PU5 - 1.8、J774A.1),在体内或体外用HBsAg颗粒脉冲处理后,在过继转移到未致敏宿主后可引发I类限制的、HBsAg特异性CTL反应。在角叉菜胶处理的小鼠中,HBsAg颗粒免疫诱导的I类限制CTL反应受到抑制,但在用同基因的、HBsAg脉冲处理的M phi免疫角叉菜胶处理的小鼠时,该反应得以恢复。通过脂质体包裹的二氯亚甲基二膦酸盐选择性清除M phi并不会抑制HBsAg颗粒免疫对H - 2d小鼠CTL反应的诱导。在体内引发I类限制CTL方面,新鲜制备的HBsAg脉冲处理的DC比脉冲处理的M phi更有效。两种类型的APC在致敏CTL中的相对重要性仍有待解决。