Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts
Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts
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DOI：
10.1182/blood-2005-09-3682
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发表时间：
2006-05-01
期刊：
影响因子：
20.3
通讯作者：
López-Botet, M
中科院分区：
文献类型：
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作者：
Gumá, M;Budt, M;López-Botet, M
在感染人巨细胞病毒（HCMV）的健康个体中，CD 94/NKG 2C（+）自然杀伤（NK）细胞增加，表明HCMV感染可能会影响NK细胞受体库。为了解决这一问题，我们分析了与HCMV感染的成纤维细胞共培养的外周血淋巴细胞（PBL）中NK细胞亚群的分布。到第10天，在一组HCMV+供体的样本中检测到INK细胞的显著增加，并且CD 94/NKG 2C（+）细胞的数量超过了CD 94/NKG 2A（+）亚群。需要成纤维细胞感染来诱导CD 94/NKG 2C（+）NK细胞的优先扩增，这与同种异体或自体成纤维细胞以及不同病毒株相当。一种CD 94特异性单克隆抗体（mAb）消除了这种效应，支持凝集素样受体的参与。用HCMV感染的细胞刺激纯化的CD 56（+）群体不增殖，但在白细胞介素-15（IL-15）存在下检测到CD 94/NKG 2C（+）亚群的扩增。HCMV缺失突变体的实验表明，CD 94/NKG 2C（+）NK细胞的应答与UL 16、UL 18和UL 40 HCMV基因无关，但当细胞感染缺乏US 2 -11基因区域的突变体时，其应答受到损害。总之，数据支持CD 94/NKG 2C与HCMV感染的成纤维细胞的相互作用，伴随着人类白细胞抗原（HLA）I类表达的抑制，促进了CD 94/NKG 2C（+）NK细胞的生长。
CD94/NKG2C(+) natural killer (NK) cells are increased in healthy individuals infected with human cytomegalovirus (HCMV), suggesting that HCMV infection may shape the INK cell receptor repertoire. To address, this question, we analyzed the distribution of NK cell subsets in peripheral blood lymphocytes (PBLs) cocultured with HCMV-infected fibroblasts. A substantial increase of INK cells was detected by day 10 in samples from a group of HCMV+ donors, and CD94/NKG2C(+) cells outnumbered the CD94/NKG2A(+) subset. Fibroblast infection was required to induce the preferential expansion of CD94/NKG2C(+) NK cells that was comparable with allogeneic or autologous fibroblasts, and different virus strains. A CD94-specific monoclonal antibody (mAb) abrogated the effect, supporting an involvement of the lectinlike receptor. Purified CD56(+) populations stimulated with HCMV-infected cells did not proliferate, but the expansion of the CD94/NKG2C(+) subset was detected in the presence of interleukin-15 (IL-15). Experiments with HCMV deletion mutants indicated that the response of CD94/NKG2C(+) NK cells was independent of the UL16, UL18, and UL40 HCMV genes, but was impaired when cells were infected with a mutant lacking the US2-11 gene region. Taken together the data support that the interaction of CD94/NKG2C with HCMV-infected fibroblasts, concomitant to the inhibition of human leukocyte antigen (HLA) class I expression, promotes an outgrowth of CD94/NKG2C(+) NK cells.