Aggarwal A, Kumar S, Jaffe R, Hone D, Gross M, Sadoff J
Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, DC 20307.
J Exp Med. 1990 Oct 1;172(4):1083-90. doi: 10.1084/jem.172.4.1083.
Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.
用含有全长伯氏疟原虫环子孢子（CS）基因的减毒鼠伤寒沙门氏菌重组体进行口服免疫，可在无抗体的情况下诱导针对伯氏疟原虫子孢子攻击的保护性免疫。我们发现这种免疫是通过诱导特异性CD8 + T细胞介导的，因为体内消除CD8 +细胞会消除保护作用。体外研究表明，这种沙门氏菌 - 伯氏疟原虫CS重组体诱导了针对跨越氨基酸242 - 253的伯氏疟原虫CS肽表位的I类限制性CD8 +细胞毒性T细胞。这与先前被鉴定为子孢子免疫诱导的细胞毒性T淋巴细胞（CTL）靶标的肽相同。构建了含有全长CS基因或由CS侧翼序列组成的无重复基因的沙门氏菌 - 恶性疟原虫CS重组体。这两种疫苗都能够诱导针对恶性疟原虫CS肽371 - 390的CD8 + CTL，该肽与子孢子和痘苗CS重组体诱导的CTL靶标相同。这些结果直接证明了诸如沙门氏菌之类的细胞内细菌诱导I类限制性CD8 + CTL的能力，并说明了CD8 + CTL在疟疾免疫中的重要性。
