Deichmann M, Kronenwett R, Haas R
Klinische Kooperationseinheit Molekulare Hamatologie/Onkologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Blood. 1997 May 15;89(10):3522-8.
CD34+ hematopoietic progenitor cells were assessed for mRNA expression of the human immunodeficiency virus type-1 (HIV-1) coreceptors CXCR-4, also termed fusin or LESTR, and CKR-5, also called CC-CKR-5 or CCR-5. The CD34+ cells were obtained from leukapheresis products of 17 patients after granulocyte colony-stimulating factor-supported cytotoxic chemotherapy. Using a two-step enrichment procedure including immunomagnetic bead separation and fluorescence-activated cell sorting, the CD34+ cells had a median purity of 99.8%. Assessing 9 CD34+ cell samples by polymerase chain reaction after reverse transcription (RT-PCR), CXCR-4 mRNA was found in all samples, whereas CKR-5 mRNA was only present in 3 samples, even though a nested PCR was used. Eight additional CD34+ cell samples were sorted according to CD4 expression. Based on a three-color immunofluorescence analysis, the mean relative fluorescence intensity of HLA-DR was smaller on CD34+/CD4+ cells in comparison with CD34+/ CD4- cells. CXCR-4 mRNA was found in 5 of 8 CD34+/CD4+ samples and in 7 of 8 CD34+/CD4- samples, whereas CKR-5 mRNA was detected in 2 CD34+/CD4+ samples and in 1 CD34+/CD4- cell sample. Looking at the total number of CD34+ cell samples examined, the proportion of specimens containing CXCR-4 mRNA was 84% in comparison with 24% of specimens positive for CKR-5 mRNA. These data suggest that CD34+/CD4+ hematopoietic progenitor cells, including true stem cell candidates, could be susceptible to HIV-1 infection. Considering the relatively low incidence of CD34+ cell samples containing CKR-5 mRNA, CD34+/CD4+ cells appear to be particularly prone for HIV-1 infection via the CXCR-4 coreceptor. Because this chemokine receptor allows T-cell-tropic HIV-1 strains to infect cells, CD34+ cells expressing CD4 and CXCR-4 might be infected by HIV-1 during later stages of the disease, following a viral phenotype switch from macrophage- to T-cell-tropic HIV-1 strains.
对CD34 +造血祖细胞进行了人类免疫缺陷病毒1型（HIV - 1）共受体CXCR - 4（也称为融合素或LESTR）和CKR - 5（也称为CC - CKR - 5或CCR - 5）的mRNA表达评估。CD34 +细胞取自17例患者在粒细胞集落刺激因子支持的细胞毒性化疗后的白细胞分离产物。采用包括免疫磁珠分离和荧光激活细胞分选的两步富集程序，CD34 +细胞的中位纯度为99.8%。通过逆转录聚合酶链反应（RT - PCR）对9个CD34 +细胞样本进行评估，发现所有样本中均有CXCR - 4 mRNA，而CKR - 5 mRNA仅在3个样本中存在，即便使用了巢式PCR。另外8个CD34 +细胞样本根据CD4表达进行分选。基于三色免疫荧光分析，与CD34 + / CD4 -细胞相比，CD34 + / CD4 +细胞上HLA - DR的平均相对荧光强度较小。在8个CD34 + / CD4 +样本中有5个以及在8个CD34 + / CD4 -样本中有7个发现了CXCR - 4 mRNA，而在2个CD34 + / CD4 +样本和1个CD34 + / CD4 -细胞样本中检测到了CKR - 5 mRNA。从所检测的CD34 +细胞样本总数来看，含有CXCR - 4 mRNA的标本比例为84%，而含有CKR - 5 mRNA的阳性标本比例为24%。这些数据表明，包括真正干细胞候选者在内的CD34 + / CD4 +造血祖细胞可能易受HIV - 1感染。考虑到含有CKR - 5 mRNA的CD34 +细胞样本发生率相对较低，CD34 + / CD4 +细胞似乎特别容易通过CXCR - 4共受体感染HIV - 1。由于这种趋化因子受体允许嗜T细胞的HIV - 1毒株感染细胞，表达CD4和CXCR - 4的CD34 +细胞可能在疾病后期被HIV - 1感染，这发生在病毒表型从巨噬细胞嗜性HIV - 1毒株转变为嗜T细胞的HIV - 1毒株之后。
