The role of CD4+ T cells in immunity to malaria sporozoites.
The role of CD4+ T cells in immunity to malaria sporozoites.
复制标题
CD4 T 细胞在疟疾子孢子免疫中的作用。
作者：
W. Weiss;M. Sedegah;J. A. Berzofsky;S. L. Hoffman
约氏疟原虫(PY)子孢子免疫BALB/c小鼠后对疟疾有较强的免疫保护作用，是研制人类疟疾疫苗的重要模型。本文探讨了CD4+细胞在诱导抗疟免疫反应中的作用。所采用的方法是在免疫前用抗CD4单抗治疗动物，导致CD4+T细胞严重耗尽。初步发现，小鼠在耗尽CD4+细胞后，没有受到子孢子免疫的保护。这些小鼠很少产生疟疾子孢子抗原的抗体，显示出这些体液反应对T细胞的强烈依赖。然而，输注高免疫血清并不能恢复抗CD4抗体处理的动物的免疫力。注射外源性IL-2也不能弥补CD4+细胞的缺失。然而，CD4+细胞的再生确实可以成功地免疫动物，这表明在没有CD4+细胞的情况下免疫并不能诱导对疟疾抗原的长期抑制。在红细胞前期，CD8+T细胞被认为是抗PY寄生虫的关键效应细胞。免疫的小鼠在耗尽了CD4+细胞的情况下，正常数量的CD8+T细胞进入了他们的肝脏。此外，它们还具有针对PY环子孢子蛋白的正常数量的脾CD8+CTL。因此，尽管CD8+细胞在没有CD4+细胞的情况下已经被激活，但它们不能保护小鼠免受疟疾的侵袭。我们的结论是，一种成功的针对红细胞前期疟疾的疫苗必须同时激活CD4+和CD8+T细胞。
BALB/c mice are strongly protected against malaria after immunization with Plasmodium yoelii (PY) sporozoites, and this is an important model for malaria vaccine development in humans. This paper explores the role of CD4+ cells in the induction of the antimalarial immune response. The method used has been to treat animals with anti-CD4 mAb before immunization, resulting in a profound depletion of CD4+ T cells. The primary finding is that mice are not protected by sporozoite immunization after depletion of CD4+ cells. Such mice make little antibody to malaria sporozoite Ag, showing the strong T-cell dependence of these humoral responses. However, infusion of hyperimmune serum does not restore immunity to anti-CD4 treated animals. Neither does injection of exogenous IL-2 compensate for the absence of CD4+ cells. However, regrowth of CD4+ cells does allow successful immunization of animals, showing that long-term suppression against malaria Ag has not been induced by immunization in the absence of CD4+ cells. It is thought that infiltrating CD8+ T cells are critical effector cells against PY parasites in the pre-erythrocytic stages. Mice immunized while depleted of CD4+ cells have normal numbers of CD8+ T cells infiltrating their livers. In addition, they have normal numbers of splenic CD8+ CTL directed at the PY circumsporozoite protein. Thus, it appears that although CD8+ cells have been activated in the absence of CD4+ cells, they cannot protect mice against malaria. We conclude that a successful vaccine against the pre-erythrocytic stages of malaria must activate both CD4+ and CD8+ T cells.