Simultaneous reconstitution of multiple cytomegalovirus-specific CD8+ cell populations with divergent functionality in hematopoietic stem-cell transplant recipients
Simultaneous reconstitution of multiple cytomegalovirus-specific CD8+ cell populations with divergent functionality in hematopoietic stem-cell transplant recipients
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DOI：
10.1086/428136
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发表时间：
2005-03-15
影响因子：
6.4
通讯作者：
Diamond, DJ
中科院分区：
文献类型：
--
作者：
Lacey, SF;Martinez, J;Diamond, DJ
一组7人巨细胞病毒（CMV）表位肽和相应的主要组织相容性1类四聚体被用来评估健康血清阳性供体和造血干细胞移植受者的细胞免疫。广泛的CMV特异性T细胞的抗原决定簇的反应被发现在几个CMV多肽，并限制了多个人类白细胞抗原等位基因。通过使用测定肽刺激后溶酶体膜蛋白LAMP-1（CD 107 a）和LAMP-2（CD 107 b）的瞬时表面水平的试验评价其细胞毒性功能。该试验可与抗原特异性CD 8（+）T淋巴细胞的四聚体染色相结合，并有可能作为细胞毒性功能的替代标志物。与识别CMV主要立即早期1表位的人群相比，对pp 65或pp 50基因产物内表位具有特异性的CD 8 + T淋巴细胞表现出显著更高的功能。同一个体内T淋巴细胞群之间的这些功能差异可能对CMV的保护有影响。
A panel of 7 human cytomegalovirus (CMV) epitope peptides and corresponding major histocompatibility class 1 tetramers was used to evaluate cellular immunity in healthy seropositive donors and in hematopoietic stem-cell transplant recipients. Broad CMV-specific T cell responses to epitopes were found within several CMV polypeptides and were restricted by multiple human leukocyte antigen alleles. Their cytotoxic functionality was evaluated by use of an assay that measures transient surface levels of lysosomal membrane proteins LAMP-1 (CD107a) and LAMP-2 (CD107b) after peptide stimulation. This assay can be combined with tetramer staining of antigen-specific CD8(+) T lymphocytes and has potential as a surrogate marker for cytotoxic function. CD8+ T lymphocytes specific for epitopes within the pp65 or pp50 gene products exhibited significantly higher functionality, compared with populations recognizing CMV major immediate early - 1 epitopes. These functional differences between T lymphocyte populations within the same individual may have implications for protection against CMV.