Long-lasting changes in the T-cell receptor V beta repertoires of CD4 memory T-cell populations in the peripheral blood of radiation-exposed people

Long-lasting changes in the T-cell receptor V beta repertoires of CD4 memory T-cell populations in the peripheral blood of radiation-exposed people
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DOI:
10.1046/j.1365-2141.2003.04520.x
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发表时间:
2003-09-01
影响因子:
6.5
通讯作者:
Kyoizumi, S
Kyoizumi, S
中科院分区:
医学2区
文献类型:
--
作者:
Kusunoki, Y;Yamaoka, M;Kyoizumi, S

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为了研究辐射诱导的T细胞耗损对人类外周CD4 T细胞群T细胞受体(TCR) Vbeta谱的长期影响,我们测量了一组原子弹幸存者中代表TCR Vbeta家族的CD4 T细胞的百分比。然后,我们估计了个体TCR Vbeta家族的表达水平与整个队列中特定TCR Vbeta家族的平均表达水平的差异程度。我们没有发现初始CD4 t细胞群体的TCR Vbeta谱发生系统性变化的证据,但记忆性CD4 t细胞TCR Vbeta家族表达水平明显偏离对应家庭的平均水平,特别是在暴露于较高剂量且爆炸时至少20岁的个体中。对同一组成年幸存者的初始和记忆CD4 t细胞池中TCR Vbeta家族表达谱的比较显示,与未暴露的对照组相比,严重暴露的幸存者中这两种类型CD4 t细胞池的TCR Vbeta谱差异更大。这些发现表明,成年后接受大量辐射剂量的个体的记忆CD4 t细胞池很可能已经(并且可能仍然)依赖于TCR Vbeta家族的多样性大大降低。
To study the long-term effects of radiation-induced T-cell depletion on the T-cell receptor (TCR) Vbeta repertoires of human peripheral CD4 T-cell populations, we measured the percentages of CD4 T cells representing each of the full range of possible TCR Vbeta families in a cohort of atomic bomb survivors. We then estimated the extent to which the expression levels for individual TCR Vbeta families differed from the average expression level for that particular TCR Vbeta family across the entire cohort. We found no evidence of a systematic change in the TCR Vbeta repertoires of the naive CD4 T-cell populations, but memory CD4 T-cell TCR Vbeta family expression levels diverged significantly from the population average for counterpart families, especially in individuals who had been exposed to higher doses and were at least 20 years of age at the time of the bombing. Comparisons of the TCR Vbeta family expression profiles in the naive and memory CD4 T-cell pools of the same group of adult survivors revealed that differences in the TCR Vbeta repertoires of these two types of CD4 T-cell pool were larger in more heavily exposed survivors than in unexposed controls. These findings suggest that the memory CD4 T-cell pools of individuals who received significant radiation doses in adulthood may well have become (and could still be) dependent upon a much less diverse complement of TCR Vbeta families than would otherwise have been the case.