Lukacs K, Kurlander R J
Department of Medicine, Duke Medical Center, Durham, NC 27719.
J Immunol. 1989 Dec 1;143(11):3731-6.
Immune CD8 cells, which play an essential role in the adoptive transfer of antilisterial immunity, can specifically lyse Listeria-bearing macrophages in vitro in an MHC-unrestricted manner. In contrast, the adoptive transfer of immunity by unseparated immune lymphocytes has been reported to be MHC-restricted. To address the restriction properties of CD8 effectors in vivo, we assessed their efficacy in protecting syngeneic and allogeneic recipients. Protection was determined by comparing the number of viable splenic Listeria in naive mice and in recipients of 60 million CD8-enriched, L3T4-depleted, Listeria-immune spleen cells, 2 days after the infusion of 10,000 Listeria. Donor cells from B6 (H-2b) mice transferred about 4 logs of protection in syngeneic recipients and more than 2 logs in allogeneic B10.A (H-2a) or B10.BR (H-2k) mice. Immune B10.A CD8 cells transferred equivalent protection to B6 mice. Protection was almost completely abrogated by the lysis or lethal irradiation of CD8 cells before transfer in vivo. On the other hand, the depletion of macrophages or NK cells did not impair adoptive transfer. By comparison, nonimmune CD8 cells from normal mice or from mice stimulated with an irrelevant Ag in vivo did not transfer substantial immunity to allogeneic recipients. We have noted previously that protective CD8 cells inhibit phagocyte accumulation in the spleen of Listeria-infected syngeneic recipients. In the present studies, we observed similar changes in adoptively immunized allogeneic mice. Reduced phagocyte accumulation may reflect Listeria-dependent lysis of infected phagocytes by immune CD8 cells. In support of this, we showed that Listeria-immune donor cells rapidly acquired the capacity to mediate Listeria-dependent, MHC-unrestricted lysis of macrophages after incubation with small amounts of IL-2 in vitro. In sum, our data establish that Listeria-immune CD8 cells can function in vivo in MHC incompatible hosts, and indirectly support the hypothesis that the destruction of infected phagocytes may be important in T cell-mediated immunity against Listeria and perhaps other intracellular pathogens.
免疫CD8细胞在抗李斯特菌免疫的过继转移中起重要作用，它能在体外以MHC非限制性方式特异性裂解携带李斯特菌的巨噬细胞。相比之下，据报道未分离的免疫淋巴细胞进行的免疫过继转移是受MHC限制的。为了研究CD8效应细胞在体内的限制特性，我们评估了它们对同基因和异基因受体的保护效果。通过比较未感染小鼠以及输注10,000个李斯特菌2天后接受6000万个富集CD8、去除L3T4、具有李斯特菌免疫的脾细胞的受体小鼠脾脏中存活李斯特菌的数量来确定保护效果。来自B6（H-2b）小鼠的供体细胞在同基因受体中转移了约4个对数级的保护，在异基因B10.A（H-2a）或B10.BR（H-2k）小鼠中转移了超过2个对数级的保护。免疫的B10.A CD8细胞向B6小鼠转移了同等程度的保护。在体内转移前对CD8细胞进行裂解或致死性照射几乎完全消除了保护作用。另一方面，去除巨噬细胞或NK细胞并不损害免疫过继转移。相比之下，来自正常小鼠或体内用无关抗原刺激的小鼠的非免疫CD8细胞不会向异基因受体转移实质性免疫。我们之前已经注意到，具有保护作用的CD8细胞会抑制李斯特菌感染的同基因受体脾脏中的吞噬细胞聚集。在本研究中，我们在免疫过继的异基因小鼠中观察到了类似的变化。吞噬细胞聚集减少可能反映了免疫CD8细胞对感染吞噬细胞依赖李斯特菌的裂解作用。支持这一点的是，我们发现李斯特菌免疫的供体细胞在体外与少量IL-2孵育后迅速获得了介导依赖李斯特菌、MHC非限制性巨噬细胞裂解的能力。总之，我们的数据表明，李斯特菌免疫的CD8细胞可以在MHC不相容的宿主体内发挥作用，并间接支持了这样一种假说，即感染吞噬细胞的破坏在T细胞介导的抗李斯特菌免疫以及可能针对其他细胞内病原体的免疫中可能很重要。
