Dittmer U, Nisslein T, Bodemer W, Petry H, Sauermann U, Stahl-Hennig C, Hunsmann G
Department for Virology and Immunology, German Primate Center, Göttingen.
Virology. 1995 Oct 1;212(2):392-7. doi: 10.1006/viro.1995.1496.
To date the vaccines most successful in the simian immunodeficiency virus (SIV) model of AIDS are live attenuated viruses. However, the virus-specific immune response induced after infection of monkeys with attenuated SIV has not been described comprehensively. Therefore, we investigated the cellular immune response of eight rhesus macaques infected with a nef deletion mutant of SIVmac32H (pC8). In contrast to monkeys infected with pathogenic SIV, pC8-infected macaques developed a virus-specific T-cell proliferation. In addition, all animals showed a proliferative T-cell response to recall antigen and mitogens. In six of eight monkeys virus-specific cytotoxic T-cells directed against different SIV polypeptides were detected. In two animals, however, the truncated nef gene reverted to full length 12 weeks after pC8 infection. These two monkeys developed hematological alterations, indicating an immunodeficiency. Simultaneously with the onset of disease the animals lost their T-cell responsiveness against recall antigens. Eight weeks later their T-cell reactivity against mitogens was also abrogated. The results indicate that live attenuated SIV induced a virus-specific cellular immune response in monkeys which might be associated with the previously reported resistance to superinfection with pathogenic SIV. Paradoxically, if the attenuated SIV reverts in vivo to a more virulent virus, the SIV-specific immune response was inefficient to prevent the onset of immunodeficiency in the animals.
迄今为止，在艾滋病的猿猴免疫缺陷病毒（SIV）模型中最成功的疫苗是减毒活病毒。然而，用减毒SIV感染猴子后诱导的病毒特异性免疫反应尚未得到全面描述。因此，我们研究了8只感染SIVmac32H的nef缺失突变体（pC8）的恒河猴的细胞免疫反应。与感染致病性SIV的猴子不同，感染pC8的猕猴产生了病毒特异性T细胞增殖。此外，所有动物对回忆抗原和丝裂原均表现出增殖性T细胞反应。在8只猴子中的6只中，检测到针对不同SIV多肽的病毒特异性细胞毒性T细胞。然而，在2只动物中，pC8感染12周后，截短的nef基因恢复为全长。这两只猴子出现血液学改变，表明存在免疫缺陷。与疾病发作同时，动物失去了对回忆抗原的T细胞反应性。8周后，它们对丝裂原的T细胞反应性也被消除。结果表明，减毒活SIV在猴子中诱导了病毒特异性细胞免疫反应，这可能与先前报道的对致病性SIV重复感染的抵抗力有关。矛盾的是，如果减毒SIV在体内恢复为毒性更强的病毒，SIV特异性免疫反应在预防动物免疫缺陷发作方面是无效的。
