T-cell dynamics after high-dose chemotherapy in adults:: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence
T-cell dynamics after high-dose chemotherapy in adults:: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence
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DOI：
10.1046/j.1365-2567.2002.01400.x
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发表时间：
2002-05-01
期刊：
影响因子：
6.4
通讯作者：
Robustelli Della Cuna, G
中科院分区：
文献类型：
--
作者：
Fagnoni, FF;Lozza, L;Robustelli Della Cuna, G
人体内T细胞耗竭后总T细胞数量的恢复伴随着CD8（+）亚群内的复杂扰动。我们的目的是阐明CD8(+) T细胞的重建，通过单独分析推定的初始CD95(-) CD28(+)，记忆CD95(+) CD28（+）和CD28(-) T细胞区室在高剂量化疗（HD-ChT）急性最大耗损后的高危乳腺癌妇女。我们发现，假定的初始CD8(+) CD95(-) CD28（+）和CD4(+) CD95(-) CD28(+) T细胞的恢复与胸腺依赖的再生途径是相容的，因为它们的恢复是缓慢的和时间依赖性的，它们的值彼此密切相关，它们的重建模式与年龄呈负相关。通过分析非初始T细胞，发现在假定的记忆T细胞和CD28(-) T细胞之间存在显著的转移。后者早期增加远远超过正常值，因此在总t细胞稳态中起关键作用，并有助于降低CD4: CD8比率。相反，假定的记忆T细胞恢复到与诊断时患者所见的值无显著差异，表明HD-ChT后该隔室可能恢复。在治疗后3-5年，幼稚T细胞持续在低水平，CD28(-) T细胞扩增，表明这种改变可能会进一步延伸。这些发现表明CD28(-) T细胞负责“盲”T细胞稳态，但支持记忆和初始T细胞分别受到调节的观点。鉴于其独特的动态，化疗患者T细胞池的定量评估应考虑初始T细胞、记忆T细胞和CD28(-) T细胞的单独分析。
Recovery of total T cell numbers after in vivo T-cell depletion in humans is accompanied by complex perturbation within the CD8(+) subset. We aimed to elucidate the reconstitution of CD8(+) T cells by separate analysis of putative naive CD95(-) CD28(+) , memory CD95(+) CD28(+) and CD28(-) T cell compartments after acute maximal depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast cancer. We found that recovery of putative naive CD8(+) CD95(-) CD28(+) and CD4(+) CD95(-) CD28(+) T cells, was compatible with a thymus-dependent regenerative pathway since their recovery was slow and time-dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non-naive T cells, a striking diversion between putative memory T cells and CD28(-) T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T-cell homeostasis, and contributed to reduce the CD4 : CD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD-ChT. At 3-5 years after treatment, naive T cells persisted at low levels, with expansion of CD28(-) T cells, suggesting that such alterations may extend further. These findings indicate that CD28(-) T cells were responsible for 'blind' T-cell homeostasis, but support the notion that memory and naive T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T-cell pools in patients undergoing chemotherapy should take into account separate analysis of naive, memory and CD28(-) T cells.