Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones.
Human CD28-CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones.
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人类 CD28-CD8 T 细胞含有大大扩展的功能性病毒特异性记忆 CTL 克隆。
DOI：
10.4049/jimmunol.162.12.7569
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发表时间：
1999
影响因子：
4.4
通讯作者：
J. Sissons
中科院分区：
文献类型：
--
作者：
Michael P. Weekes;Andrew J. Carmichael;Mark R. Wills;Kim Mynard;J. Sissons
在出生时，几乎所有的人外周血CD 8 + T细胞表达共刺激分子CD 28。随着年龄的增长，缺乏CD 28的CD 8 + T细胞的比例增加。由于CD 28-CD 8 + T细胞的抗原特异性以前没有被定义，我们研究了CD 28-CD 8 + T细胞对针对两种人类持久性病毒（人类CMV（HCMV）和HIV）的记忆性CD 8 + CTL应答的贡献。从健康病毒携带者的PBMC中，我们产生了多个对定义的病毒肽特异性的独立CTL克隆，并对其TCR β链进行测序。我们设计了与每个β链高变序列互补的克隆型寡核苷酸，并定量了PBMC中单个免疫显性CTL克隆的大小。一些单个CTL克隆非常大，占PBMC中所有CD 8 + T细胞的3.1%，并且通常维持在稳定水平数月。单个病毒特异性CTL克隆在纯化的CD 28-细胞中始终比在整个CD 8+群体中更丰富。由于CD 28-CD 8+细胞作为一个群体已被报道增殖不良，在有丝分裂原的反应，我们研究了这些病毒特异性CD 28- CTL克隆的功能，通过定量的频率肽特异性CTL前体使用有限稀释分析。CD 28-CD 8 + T细胞含有高频率的对HCMV或HIV的肽特异性的功能性记忆CTL前体，通常高于作为整体的CD 8 + T细胞群体。我们的结论是，在无症状的HCMV和HIV感染，人CD 28-CD 8 + T细胞含有高频率的功能性病毒特异性记忆CTL克隆。
At birth, almost all human peripheral blood CD8+ T cells express the costimulatory molecule CD28. With increasing age, the proportion of CD8+ T cells that lack CD28 increases. Because the Ag specificity of CD28-CD8+ T cells has not previously been defined, we studied the contribution of CD28-CD8+ T cells to the memory CD8+ CTL response against two human persistent viruses, human CMV (HCMV) and HIV. From PBMC of healthy virus carriers we generated multiple independent CTL clones specific for defined viral peptides and sequenced their TCR beta-chains. We designed clonotypic oligonucleotides complementary to each beta-chain hypervariable sequence and quantified the size of individual immunodominant CTL clones in PBMC. Some individual CTL clones were very large, comprising up to 3.1% of all CD8+ T cells in PBMC, and were generally maintained at a stable level for months. Individual virus-specific CTL clones were consistently more abundant in purified CD28- cells than in the CD8+ population as a whole. Because CD28-CD8+ cells as a population have been reported to proliferate poorly in response to mitogen, we studied the function of these virus-specific CD28- CTL clones by quantifying the frequency of peptide-specific CTL precursors using limiting dilution analysis. CD28-CD8+ T cells contained high frequencies of functional memory CTL precursors specific for peptides of HCMV or HIV, generally higher than in the CD8+ T cell population as a whole. We conclude that in asymptomatic HCMV and HIV infection, human CD28-CD8+ T cells contain high frequencies of functional virus-specific memory CTL clones.
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影响因子：
4.4
作者：
E. Kabat;Te Wu Tai Te Wu-Te-Wu-Tai-Te-Wu-2244585577
通讯作者：
E. Kabat;Te Wu Tai Te Wu-Te-Wu-Tai-Te-Wu-2244585577
影响因子：
4.4
作者：
J. Monteiro;F. Batliwalla;Harry Ostrer;Peter K. Gregersen
通讯作者：
J. Monteiro;F. Batliwalla;Harry Ostrer;Peter K. Gregersen
影响因子：
4.4
作者：
Dorothy E. Lewis;D. N. Tang;A. Adu-Oppong;Wendy Schober;J. Rodgers
通讯作者：
Dorothy E. Lewis;D. N. Tang;A. Adu-Oppong;Wendy Schober;J. Rodgers
影响因子：
2.7
作者：
Batliwalla, F;Monteiro, J;Gregersen, PK
通讯作者：
Gregersen, PK
影响因子：
56.9
作者：
Ogg, GS;Jin, X;McMichael, AJ
通讯作者：
McMichael, AJ