Abstract：
Fibrocytes were reported to be host cells for HIV-1, but the immunological recognition of HIV-1-infected fibrocytes has not been studied. Here, we investigated the recognition of HIV-1-infected fibrocytes by HIV-1-specific CD8+ T cells. CD8+ T cells specific for five HIV-1 epitopes (HLA-A*24:02-restricted, HLA-B*52:01-restricted, and HLA-C*12:02-restricted epitopes) produced IFN-γ and expressed CD107a after coculture with HIV-1-infected fibrocytes. HIV-1-infected fibrocytes were effectively killed by HIV-1-specific CD8+ T cells. Although it is well known that HIV-1 Nef-mediated downregulation of HLA-A and HLA-B critically affects the T cell recognition of HIV-1-infected CD4+ T cells and HIV-1-infected macrophages, Nef downregulated HLA-A, but not HLA-B, in HIV-1-infected fibrocytes. These findings suggested that HIV-1-specific CD8+ T cells could recognize HIV-1-infected fibrocytes more strongly than HIV-1-infected CD4+ T cells or HIV-1-infected macrophages. HIV-1-infected fibrocytes were also recognized by HIV-1-specific HLA-DR-restricted T cells, indicating that HIV-1-infected fibrocytes can present HIV-1 epitopes to helper T cells. Collectively, these findings suggest that fibrocytes have an important role as antigen-presenting cells during HIV-1 infection. The present study demonstrates effective recognition of HIV-1-infected fibrocytes by HIV-1-specific T cells and suggests possible roles of fibrocytes in the induction and maintenance of HIV-1-specific T cells.
OBJECTIVE: Fibrocytes were identified as unique hematopoietic cells with the features of both macrophages and fibroblasts and were demonstrated to be host cells for HIV-1. However, T cell recognition of HIV-1-infected fibrocytes has not been studied. We investigated the recognition of HIV-1-infected fibrocytes by HIV-1-specific T cells. HIV-1-infected fibrocytes were effectively recognized and killed by CD8+ T cells specific for HIV-1 epitopes presented by HLA-A, HLA-B, or HLA-C and were recognized by HIV-1-specific HLA-DR-restricted CD4+ T cells. HIV-1 Nef-mediated downregulation of HLA-A and HLA-B was found in HIV-1-infected CD4+ T cells, whereas Nef did not downregulate HLA-B in HIV-1-infected fibrocytes. These results suggest that HIV-1-specific CD8+ T cells recognize HIV-1-infected fibrocytes more strongly than HIV-1-infected CD4+ T cells. The present study suggests the importance of fibrocytes in the induction and maintenance of HIV-1-specific T cells.
OBJECTIVE: Fibrocytes were identified as unique hematopoietic cells with the features of both macrophages and fibroblasts and were demonstrated to be host cells for HIV-1. However, T cell recognition of HIV-1-infected fibrocytes has not been studied. We investigated the recognition of HIV-1-infected fibrocytes by HIV-1-specific T cells. HIV-1-infected fibrocytes were effectively recognized and killed by CD8+ T cells specific for HIV-1 epitopes presented by HLA-A, HLA-B, or HLA-C and were recognized by HIV-1-specific HLA-DR-restricted CD4+ T cells. HIV-1 Nef-mediated downregulation of HLA-A and HLA-B was found in HIV-1-infected CD4+ T cells, whereas Nef did not downregulate HLA-B in HIV-1-infected fibrocytes. These results suggest that HIV-1-specific CD8+ T cells recognize HIV-1-infected fibrocytes more strongly than HIV-1-infected CD4+ T cells. The present study suggests the importance of fibrocytes in the induction and maintenance of HIV-1-specific T cells.
摘要：
据报道，纤维细胞是HIV-1的宿主细胞，但尚未研究HIV-1感染的纤维细胞的免疫识别。这里,我们研究了HIV-1特异性CD8+T细胞对HIV-1感染的纤维细胞的识别.对五个HIV-1表位具有特异性的CD8T细胞（HLA-A*24：02限制性，HLA-B*52:01限制，和HLA-C*12：02限制性表位）在与HIV-1感染的纤维细胞共培养后产生IFN-γ并表达CD107a。HIV-1感染的纤维细胞被HIV-1特异性CD8+T细胞有效杀死。尽管众所周知，HIV-1Nef介导的HLA-A和HLA-B下调严重影响HIV-1感染的CD4+T细胞和HIV-1感染的巨噬细胞的T细胞识别，Nef下调HLA-A,但不是HLA-B,在HIV-1感染的纤维细胞中。这些发现表明，HIV-1特异性CD8T细胞可以比HIV-1感染的CD4T细胞或HIV-1感染的巨噬细胞更强烈地识别HIV-1感染的纤维细胞。HIV-1感染的纤维细胞也被HIV-1特异性HLA-DR限制性T细胞识别，这表明HIV-1感染的纤维细胞可以将HIV-1表位呈递给辅助性T细胞。总的来说，这些发现提示纤维细胞在HIV-1感染过程中作为抗原呈递细胞具有重要作用.本研究证明了HIV-1特异性T细胞对HIV-1感染的纤维细胞的有效识别，并提示了纤维细胞在HIV-1特异性T细胞的诱导和维持中的可能作用。
目的：纤维细胞被鉴定为具有巨噬细胞和成纤维细胞特征的独特造血细胞，并被证明是HIV-1的宿主细胞。然而,尚未研究HIV-1感染的纤维细胞的T细胞识别。我们研究了HIV-1特异性T细胞对HIV-1感染的纤维细胞的识别。HIV-1感染的纤维细胞被HLA-A呈递的HIV-1表位特异性CD8+T细胞有效识别和杀死。HLA-B,或HLA-C，并被HIV-1特异性HLA-DR限制性CD4+T细胞识别。在HIV-1感染的CD4+T细胞中发现了HIV-1Nef介导的HLA-A和HLA-B的下调,而Nef在HIV-1感染的纤维细胞中不下调HLA-B。这些结果表明，HIV-1特异性CD8T细胞比HIV-1感染的CD4T细胞更强烈地识别HIV-1感染的纤维细胞。本研究表明纤维细胞在HIV-1特异性T细胞的诱导和维持中的重要性。
目的：纤维细胞被鉴定为具有巨噬细胞和成纤维细胞特征的独特造血细胞，并被证明是HIV-1的宿主细胞。然而,尚未研究HIV-1感染的纤维细胞的T细胞识别。我们研究了HIV-1特异性T细胞对HIV-1感染的纤维细胞的识别。HIV-1感染的纤维细胞被HLA-A呈递的HIV-1表位特异性CD8+T细胞有效识别和杀死。HLA-B,或HLA-C，并被HIV-1特异性HLA-DR限制性CD4+T细胞识别。在HIV-1感染的CD4+T细胞中发现了HIV-1Nef介导的HLA-A和HLA-B的下调,而Nef在HIV-1感染的纤维细胞中不下调HLA-B。这些结果表明，HIV-1特异性CD8T细胞比HIV-1感染的CD4T细胞更强烈地识别HIV-1感染的纤维细胞。本研究表明纤维细胞在HIV-1特异性T细胞的诱导和维持中的重要性。
