CD8+ T-CELLS (CYTOTOXIC/SUPPRESSORS) ARE REQUIRED FOR PROTECTION IN MICE IMMUNIZED WITH MALARIA SPOROZOITES

CD8+ T-CELLS (CYTOTOXIC/SUPPRESSORS) ARE REQUIRED FOR PROTECTION IN MICE IMMUNIZED WITH MALARIA SPOROZOITES
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DOI:
10.1073/pnas.85.2.573
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发表时间:
1988-01-01
影响因子:
11.1
通讯作者:
GOOD, MF
GOOD, MF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
WEISS, WR;SEDEGAH, M;GOOD, MF

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在最近的人类和小鼠疟疾孢子子疫苗试验中,针对孢子子外壳蛋白的抗体仅对孢子子的攻击提供了适度的保护。相比之下,辐照的孢子体可以保护小鼠免受大量孢子体感染。有证据表明,这些小鼠的免疫是由T细胞介导的。为了确定免疫机制,我们使用CD4或CD8分子特异性单克隆抗体选择性地消耗孢子子免疫小鼠的t细胞亚群。虽然体内CD4+ T细胞的消耗不会降低免疫力,但CD8+ T细胞的消耗会消除保护作用。单克隆抗体处理不影响抗孢子虫抗体水平。我们的数据表明,细胞毒性T细胞对大量孢子虫的免疫至关重要,并建议疫苗开发应重新定向,以刺激细胞和体液免疫。
In recent malaria sporozoite vaccine trials in humans and mice, antibodies to the sporozoite coat protein have given only modest protection against sporozoite challenge. In contrast, irradiated sporozoites can protect mice against massive sporozoite infections. Evidence suggests that immunity in these mice is mediated by T cells. To identify the mechanism of immunity, we used monoclonal antibodies specific for either the CD4 or CD8 molecule to selectively deplete sporozoite-immunized mice of T-cell subsets. Though in vivo depletion of CD4+ T cells did not reduce immunity, depletion of CD8+ T cells abolished protection. Monoclonal antibody treatment did not affect anti-sporozoite antibody levels. Our data indicate that cytotoxic T cells are critical for immunity to large numbers of sporozoites and suggest that vaccine development should be reoriented toward stimulating cellular as well as humoral immunity.