HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi

HIV-1-specific mucosal CD8+ lymphocyte responses in the cervix of HIV-1-resistant prostitutes in Nairobi
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DOI:
10.4049/jimmunol.164.3.1602
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发表时间:
2000-02-01
影响因子:
4.4
通讯作者:
Rowland-Jones, SL
Rowland-Jones, SL
中科院分区:
医学2区
文献类型:
--
作者:
Kaul, R;Plummer, FA;Rowland-Jones, SL

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了解HIV高度暴露的个体如何避免持续感染对MV疫苗设计至关重要。有证据表明,粘膜免疫,特别是病毒特异性CTL,可能是至关重要的保护性获得性艾滋病毒感染。因此,我们在内罗毕的一个高度暴露于艾滋病毒但持续血清阴性的女性性工作者亚组的宫颈单核细胞中寻找艾滋病毒特异性CD 8(+)T细胞的存在,使用酶联免疫斑点试验,使用来自HIV-1耐药和HIV-2耐药患者的血液和宫颈的效应细胞,测量IFN-γ释放对已知I类HLA限制性CTL表位肽的应答。受感染的性工作者和低风险的未受感染的对照。16名抵抗性工作者中有11名在子宫颈中有HIV特异性CD 8(+)T细胞,血液中也有类似数量的可检测到的反应。当在同一个体中检测到血液和宫颈反应时,反应的特异性相似。在低风险对照供体中未检测到宫颈或血液反应。HIV抵抗性工作者宫颈中HIV特异性CD 8(+)T细胞频率略高于血液,而HIV感染者宫颈反应频率明显低于血液,因此HIV抵抗性工作者宫颈反应相对富集。在HIV-1耐药性工作者的生殖器粘膜中没有可检测到的HIV感染的情况下,HIV特异性CD 8(+)T细胞反应可能在针对异性HIV-I传播的保护性免疫中发挥重要作用。
Understanding how individuals with a high degree of HIV exposure avoid persistent infection is paramount to MV vaccine design. Evidence suggests that mucosal immunity, particularly virus-specific CTL, could be critically important in protection against sexually acquired HIV infection. Therefore, we have looked for the presence of HIV-specific CD8(+) T cells in cervical mononuclear cells from a subgroup of highly HIV-exposed but persistently seronegative female sex workers in Nairobi, An enzyme-linked immunospot assay was used to measure IFN-gamma release in response to known class I HLA-restricted CTL epitope peptides using effector cells from the blood and cervix of HIV-1-resistant and -infected sex workers and from lower-risk uninfected controls. Eleven of 16 resistant sex workers had HIV-specific CD8(+) T cells in the cervix, and a similar number had detectable responses in blood. Where both blood and cervical responses were detected in the same individual, the specificity of the responses was similar. Neither cervical nor blood responses were detected in lower-risk control donors. HIV-specific CD8(+) T cell frequencies in the cervix of HIV-resistant sex workers were slightly higher than in blood, while in HIV-infected donor cervical response frequencies were markedly lower than blood, so that there was relative enrichment of cervical responses in HIV-resistant compared with HIV-infected donors. HIV-specific CD8(+) T cell responses in the absence of detectable HIV infection in the genital mucosa of HIV-1-resistant sex workers may be playing an important part in protective immunity against heterosexual HIV-I transmission.