Vignali D A, Crocker P, Bickle Q D, Cobbold S, Waldmann H, Taylor M G
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, U.K.
Immunology. 1989 Aug;67(4):466-72.
The role of CD4+ (L3/T4+) and CD8+ (Lyt-2+) T cells in immunity to Schistosoma mansoni induced by 20 krad-irradiated and Ro 11-terminated infections in mice was investigated directly by in vivo depletion of these subsets with cytotoxic rat monoclonal antibodies (mAb). Effective physical depletion was demonstrated by flow cytometric analysis and immunohistochemical staining. Functional depletion of helper activity following anti-CD4 treatment was indicated by an abrogation of concanavalin A(Con A)-induced colony-stimulating factor (CSF) release, while anti-CD8 treatment had no effect in these assays. Pre-existing S. mansoni-specific antibody levels were unaffected by anti-CD4 and anti-CD8 treatment. In vivo depletion of CD4+ T cells resulted in a dramatic reduction in immunity induced by one (up to 100%) and two (up to 70%) vaccinations with 20 krad-irradiated cercariae and also of resistance induced by Ro 11-attenuated infections (up to 100%). Depletion of CD8+ T cells had no effect on resistance induced by any of the vaccination protocols investigated. A correlation was observed between resistance and T cell-induced, macrophage-mediated killing of schistosomula in vitro, both of which were abrogated following anti-CD4 treatment but were unaffected by CD8+ T-cell depletion. The possible role of CD4+ T cells in vivo and the implications for vaccine development are discussed.
通过用细胞毒性大鼠单克隆抗体（mAb）在体内清除这些亚群，直接研究了CD4+（L3/T4+）和CD8+（Lyt-2+）T细胞在小鼠中由20 krad照射和Ro 11终止感染诱导的对曼氏血吸虫免疫中的作用。通过流式细胞术分析和免疫组织化学染色证明了有效的物理清除。抗CD4治疗后辅助活性的功能清除通过伴刀豆球蛋白A（Con A）诱导的集落刺激因子（CSF）释放的消除来表明，而抗CD8治疗在这些试验中没有效果。预先存在的曼氏血吸虫特异性抗体水平不受抗CD4和抗CD8治疗的影响。体内清除CD4+ T细胞导致用20 krad照射的尾蚴进行一次（高达100%）和两次（高达70%）疫苗接种诱导的免疫力以及Ro 11减毒感染诱导的抵抗力（高达100%）显著降低。清除CD8+ T细胞对所研究的任何疫苗接种方案诱导的抵抗力没有影响。在体外观察到抵抗力与T细胞诱导的、巨噬细胞介导的对血吸虫幼虫的杀伤之间存在相关性，抗CD4治疗后两者均被消除，但不受CD8+ T细胞清除的影响。讨论了CD4+ T细胞在体内的可能作用及其对疫苗开发的意义。
