Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus
Induction of vigorous cytotoxic T-lymphocyte responses by live attenuated simian immunodeficiency virus
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DOI：
10.1128/jvi.71.10.7711-7718.1997
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发表时间：
1997-10-01
影响因子：
5.4
通讯作者：
Desrosiers, RC
中科院分区：
文献类型：
--
作者：
Johnson, RP;Glickman, RL;Desrosiers, RC
尽管猴免疫缺陷病毒（Sn）减毒活疫苗株已被证明在保护猕猴免受致病性SIV毒株的攻击方面非常有效，但对这些疫苗诱导的保护性免疫机制知之甚少。我们在感染SIVmac239 Delta nef（缺乏nef）或STVmac239 Delta 3（缺乏nef， vpr和U3上游序列）的动物中检测了细胞毒性t淋巴细胞（CTL）对SIV的反应。为了提高检测sn特异性CTL活性，我们用自体b淋巴母细胞样细胞系刺激外周血单个核细胞，这些细胞系被表达SIV蛋白的重组痘苗病毒感染，随后用补骨脂素和紫外线灭活。慢性感染SIV239 Delta nef或SN239 Delta 3的动物对SIV Gag和Env蛋白产生强烈的CTL反应，这种CTL活性是主要的组织相容性类，受CD8(+) T淋巴细胞的限制和介导，CTL反应在感染后持续相对较高的水平超过6 Sears，限制性稀释前体频率测定表明，sn特异性CTL的频率高达每10万个细胞234个CTL前体。急性感染SN239 Delta nef的动物在感染后第14天出现CTL活性，与病毒载量下降一致，急性感染SIV239 Delta 3的动物在感染后4周内出现CTL反应，因此，接种SN239 Delta nef或SN239 Delta 3的幼动物或成年动物可诱导强烈的CTL反应，这种反应在感染过程早期出现，并在单次接种病毒后持续数年。
Although live attenuated vaccine strains of simian immunodeficiency virus (Sn) have proven highly effective in protecting macaques against challenge with pathogenic SIV strains, little is known about the mechanisms of protective immunity induced by these vaccines, We examined cytotoxic T-lymphocyte (CTL) responses against SIV in animals infected with SIVmac239 Delta nef (deficient in nef) or STVmac239 Delta 3 (deficient in nef, vpr, and upstream sequences in U3), To enhance detection of SN-specific CTL activity, we stimulated peripheral blood mononuclear cells with autologous B-lymphoblastoid cell lines which had been infected with recombinant vaccinia viruses expressing SIV proteins and subsequently inactivated with psoralen and UV light. Animals chronically infected with SIV239 Delta nef or SN239 Delta 3 mounted vigorous CTL responses against the SIV Gag and Env proteins, This CTL activity was major histocompatibility class restricted and mediated by CD8(+) T lymphocytes, CTL responses persisted at relatively high levels for more than 6 Sears after infection, Limiting dilution precursor frequency assays demonstrated that the frequency of SN-specific CTLs was as high as 234 CTL precursors per 100,000 cells, Animals acutely infected with SN239 Delta nef developed CTL activity by day 14 after infection, coincident with decreases in viral load, Animals acutely infected with SIV239 Delta 3 developed CTL responses within 4 weeks of infection, Thus, vaccination of juvenile or adult animals with SN239 Delta nef or SN239 Delta 3 results in the induction of a vigorous CTL response which arises early in the course of infection and persists for gears after a single inoculation of virus.