Cromwell M A, Veazey R S, Altman J D, Mansfield K G, Glickman R, Allen T M, Watkins D I, Lackner A A, Johnson R P
Divisions of Immunology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772, USA.
J Virol. 2000 Sep;74(18):8762-6. doi: 10.1128/jvi.74.18.8762-8766.2000.
Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8(+) lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor alpha4beta7 and traffic to the intestinal mucosa. SIV-specific CD8(+) T cells expressing alpha4beta7 were detected in peripheral blood and intestine of macaques infected with attenuated SIV. In contrast, virus-specific T cells in blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus Ankara regimen did not express alpha4beta7. These results demonstrate the selective induction of SIV-specific CD8(+) T lymphocytes expressing alpha4beta7 by a vaccine approach that replicates in mucosal tissue and suggest that induction of virus-specific lymphocytes that are able to home to mucosal sites may be an important characteristic of a successful AIDS vaccine.
在免疫系统的黏膜及全身各部分诱导病毒特异性T细胞应答很可能是有效艾滋病疫苗的关键特性。我们研究了用减毒猿猴免疫缺陷病毒(SIV)免疫恒河猴所诱导的病毒特异性CD8(+)淋巴细胞是否表达黏膜归巢受体α4β7并迁移至肠道黏膜,这种方法在引发针对黏膜攻击的保护方面非常有效。在感染减毒SIV的猕猴的外周血和肠道中检测到了表达α4β7的SIV特异性CD8(+) T细胞。相比之下,通过联合DNA修饰的安卡拉痘苗病毒方案进行皮肤免疫的动物血液中的病毒特异性T细胞不表达α4β7。这些结果表明,通过在黏膜组织中复制的疫苗方法可选择性诱导表达α4β7的SIV特异性CD8(+) T淋巴细胞,这表明诱导能够归巢至黏膜部位的病毒特异性淋巴细胞可能是成功的艾滋病疫苗的一个重要特征。