The LCMV gp33-specific memory T cell repertoire narrows with age.
The LCMV gp33-specific memory T cell repertoire narrows with age.
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DOI：
10.1186/1742-4933-9-17
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发表时间：
2012-08-15
期刊：
影响因子：
--
通讯作者：
Frelinger JA
中科院分区：
文献类型：
--
作者：
Bunztman A;Vincent BG;Krovi H;Steele S;Frelinger JA
小鼠对LCMV的记忆反应持续数月至数年，表位特异性CD8 T细胞的数量仅略有减少。这种长期存在与对致命的LCMV疾病的抵抗力有关。相对于对记忆细胞数量和表面表型的研究，对这些细胞中TCR使用的多样性的关注相对较少。CD8+ T细胞反应只有少数克隆具有相同的特异性被认为是相对无效的，可能是由于病毒相对容易逃逸。因此，广泛的多克隆应答与有效的抗病毒CD8+ T细胞应答相关。在本文中，我们发现原发性CD8+ T细胞对LCMV gp33-41表位的反应是非常多样化的。随着时间的推移，虽然在gp33-四聚体+ T细胞的数量方面反应仍然强劲，但反应的多样性变得越来越少。引人注目的是，在感染后26个月，这种反应主要由少数TCRβ序列主导。此外，值得注意的是，gp33特异性CD8+ T细胞在感染后15和22个月被高低四聚体结合群体分类。高、低四聚体结合细胞具有相当的多样性，且无论测试时间长短，均以少量克隆为主。感染26个月后，NP396特异性CD8+ T细胞也出现了类似的限制性分布。在四amerhi和四amerlo结合群体中均发现相同的TCRVβ序列。最后，我们没有看到gp33特异性反应中存在公开克隆的证据。没有在多个小鼠中发现CDR3序列。这些数据表明，LCMV感染后，CD8+ gp33特异性CD8 T细胞反应受到高度限制，多样性大大缩小。这种储备的缩小可能导致在衰老过程中所见的免疫反应逐渐失效。
The memory response to LCMV in mice persists for months to years with only a small decrease in the number of epitope specific CD8 T cells. This long persistence is associated with resistance to lethal LCMV disease. In contrast to studies focused on the number and surface phenotype of the memory cells, relatively little attention has been paid to the diversity of TCR usage in these cells. CD8+ T cell responses with only a few clones of identical specificity are believed to be relatively ineffective, presumably due to the relative ease of virus escape. Thus, a broad polyclonal response is associated with an effective anti-viral CD8+ T cell response. In this paper we show that the primary CD8+ T cell response to the LCMV gp33-41 epitope is extremely diverse. Over time while the response remains robust in terms of the number of gp33-tetramer+ T cells, the diversity of the response becomes less so. Strikingly, by 26 months after infection the response is dominated by a small number TCRβ sequences. In addition, it is of note the gp33 specific CD8+ T cells sorted by high and low tetramer binding populations 15 and 22 months after infection. High and low tetramer binding cells had equivalent diversity and were dominated by a small number of clones regardless of the time tested. A similar restricted distribution was seen in NP396 specific CD8+ T cells 26 months after infection. The identical TCRVβ sequences were found in both the tetramerhi and tetramerlo binding populations. Finally, we saw no evidence of public clones in the gp33-specific response. No CDR3 sequences were found in more than one mouse. These data show that following LCMV infection the CD8+ gp33-specific CD8 T cell response becomes highly restricted with enormous narrowing of the diversity. This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging.
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影响因子：
4.4
作者：
LeMaoult, J;Messaoudi, I;Nikolich-Zugich, J
通讯作者：
Nikolich-Zugich, J
影响因子：
4.8
作者：
Jost, Lou
通讯作者：
Jost, Lou
DOI：
10.1098/rspb.2011.0453
发表时间：
2011-11-22
影响因子：
4.7
作者：
Graw, Frederik;Richter, Kirsten;Regoes, Roland R.
通讯作者：
Regoes, Roland R.
DOI：
10.1084/jem.188.11.1993
发表时间：
1998-12-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.182.2.784
发表时间：
2009-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ahmed M;Lanzer KG;Yager EJ;Adams PS;Johnson LL;Blackman MA
通讯作者：
Blackman MA