巨细胞病毒感染的成纤维细胞自然杀伤中HLA - DR +辅助细胞的需求

Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts.

作者信息

Bandyopadhyay S, Perussia B, Trinchieri G, Miller D S, Starr S E

出版信息

J Exp Med. 1986 Jul 1;164(1):180-95. doi: 10.1084/jem.164.1.180.

DOI:10.1084/jem.164.1.180

PMID:3014033

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2188221/

Abstract

The role of HLA-DR+ cells in NK activity against CMV-infected FS4 foreskin fibroblasts and K562 erythroleukemia cells was examined. When nonadherent PBMC were depleted of either HLA-DR+ or Leu-11b+ cells by treatment with mAbs plus C, NK activity against CMV-FS4 target cells was markedly reduced. In contrast, depletion of HLA-DR+ cells had no effect on NK activity against K562 target cells. When HLA-DR-depleted cells were added to Leu-11b-depleted cells, NK activity against CMV-FS4 was restored. Negative selection experiments indicated that the HLA-DR+ cells contributing to NK activity against CMV-FS4 are not B or T cells, while negative and positive selection experiments excluded a role for monocytes. Experiments in which HLA-DR- and Leu-11b- cells were mixed in varying proportions indicated that NK(CMV-FS4) is mediated by Leu-11b+ cells, while HLA-DR+ cells provide an accessory function. Irradiation (50 GY) abolished the NK effector function of Leu-11b+ cells, but not the accessory function of HLA-DR+ cells. The NK activity against CMV-FS4 of HLA-DR- cells was restored by the addition of rIFN-alpha or of cell-free supernatants generated by coculturing PBMC or Leu-11b- cells with CMV-FS4. The ability of these supernatants to restore NK activity of HLA-DR- cells was completely abrogated by the addition of neutralizing amounts of antibody to IFN-alpha. In related experiments, neutralization of IFN-alpha in NK assays had little or no effect on NK activity against CMV-FS4, suggesting that the accessory function of HLA-DR+ cells might be mediated by alternative mechanisms in addition to the secretion of extracellular IFN-alpha.

摘要

研究了HLA - DR⁺细胞在自然杀伤细胞（NK）针对巨细胞病毒（CMV）感染的FS4包皮成纤维细胞和K562红白血病细胞的活性中的作用。当用单克隆抗体加补体处理使非贴壁外周血单核细胞（PBMC）中的HLA - DR⁺或Leu - 11b⁺细胞被清除时，针对CMV - FS4靶细胞的NK活性显著降低。相比之下，清除HLA - DR⁺细胞对针对K562靶细胞的NK活性没有影响。当将去除HLA - DR的细胞添加到去除Leu - 11b的细胞中时，针对CMV - FS4的NK活性得以恢复。阴性选择实验表明，对CMV - FS4具有NK活性的HLA - DR⁺细胞不是B细胞或T细胞，而阴性和阳性选择实验排除了单核细胞的作用。将HLA - DR⁻和Leu - 11b⁻细胞以不同比例混合的实验表明，NK（CMV - FS4）由Leu - 11b⁺细胞介导，而HLA - DR⁺细胞提供辅助功能。照射（50戈瑞）消除了Leu - 11b⁺细胞的NK效应功能，但没有消除HLA - DR⁺细胞的辅助功能。添加重组干扰素 - α（rIFN - α）或通过将PBMC或Leu - 11b⁻细胞与CMV - FS4共培养产生的无细胞上清液可恢复HLA - DR⁻细胞对CMV - FS4的NK活性。加入中和量的抗干扰素 - α抗体可完全消除这些上清液恢复HLA - DR⁻细胞NK活性的能力。在相关实验中，在NK测定中中和干扰素 - α对针对CMV - FS4的NK活性几乎没有影响，这表明HLA - DR⁺细胞的辅助功能可能除了分泌细胞外干扰素 - α外还由其他机制介导。