Zinkernagel R
Departement Pathologie, Universität Zürich.
Verh Dtsch Ges Pathol. 1994;78:166-70.
Cytotoxic effectors-CD8+ T cells protect hosts against cytopathic viruses. CD8+ T cell mediated lysis of host cells infected with non-cytopathic viruses may lead to tissue disease causing damage as is the case in hepatitis B virus infections in men or lymphocytic choriomeningitis virus (LCMV) infections in mice. In a mouse model it was demonstrated that virus induced immunodeficiency by LCMV was not caused by the virus directly but rather by immunopathological consequences of anti-LCMV CD8+ T cells destroying LCMV-infected antigen-presenting cells and macrophages. These results may suggest that HIV induced immunodeficiency could similarly be caused by immunopathology because 1. HIV has not been demonstrated to be cytopathic in vivo. 2. CD8+ T cells control HIV infection efficiently for a longtime and 3. only few CD4+ T cells but many macrophages, monocytes and dendritic cells are productively HIV infected. Therefore AIDS may be the result of specific CD8+ T cells destroying antigen presenting cells and effector/macrophages/monocytes thereby causing immunosuppression and inability to control intracellular infections. Compared to the view that HIV is cytopathic, the immunopathological view of AIDS suggests obviously different vaccine and therapy strategies.
细胞毒性效应细胞——CD8 + T细胞可保护宿主抵御细胞病变性病毒。CD8 + T细胞介导的对感染非细胞病变性病毒的宿主细胞的裂解,可能会导致组织疾病并造成损害,就像人类感染乙肝病毒或小鼠感染淋巴细胞性脉络丛脑膜炎病毒(LCMV)那样。在一个小鼠模型中,研究表明LCMV诱导的病毒免疫缺陷并非由病毒直接引起,而是由抗LCMV CD8 + T细胞破坏LCMV感染的抗原呈递细胞和巨噬细胞的免疫病理后果所致。这些结果可能表明,HIV诱导的免疫缺陷同样可能是由免疫病理学引起的,因为:1. 尚未证明HIV在体内具有细胞病变性;2. CD8 + T细胞能长期有效地控制HIV感染;3. 只有少数CD4 + T细胞被HIV有效感染,但许多巨噬细胞、单核细胞和树突状细胞都被HIV有效感染。因此,艾滋病可能是特定CD8 + T细胞破坏抗原呈递细胞和效应细胞/巨噬细胞/单核细胞的结果,从而导致免疫抑制和无法控制细胞内感染。与认为HIV具有细胞病变性的观点相比,艾滋病的免疫病理学观点显然提示了不同的疫苗和治疗策略。