EVIDENCE FOR ACCESSORY CELL-FUNCTION BY CLASS-II MHC ANTIGEN-EXPRESSING AIRWAY EPITHELIAL-CELLS

EVIDENCE FOR ACCESSORY CELL-FUNCTION BY CLASS-II MHC ANTIGEN-EXPRESSING AIRWAY EPITHELIAL-CELLS
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DOI:
10.1165/ajrcmb/4.4.320
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发表时间:
1991-04-01
影响因子:
6.4
通讯作者:
MAYER, L
MAYER, L
中科院分区:
医学1区
文献类型:
--
作者:
KALB, TH;CHUANG, MT;MAYER, L

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主要组织相容性复合体(MHC)II类抗原的表达是抗原呈递中辅助细胞功能的需要。 最近的报道已经证明了人支气管上皮细胞上存在II类抗原。 在本研究中,免疫组化染色显示人类气道上皮细胞从两个不同的粘膜部位(叶支气管和鼻甲)的HLA-DR。 为了确定气道上皮细胞是否具有允许其与T淋巴细胞同源相互作用的功能性II类分子,将从这些部位分离的细胞用于混合淋巴细胞培养物(MLR)中,作为辅助细胞功能的体外模型。 新鲜分离的细胞(11个支气管/3个鼻甲)刺激同种异体T淋巴细胞(刺激指数[S.I.] = 9.3 [平均值];与单独的T细胞相比,P < 0.001)。 为了评估污染的传统辅助细胞的潜在作用,支气管上皮细胞分离株首先在无血清、补充生长因子的培养基中预孵育,该培养基在MLR培养之前功能性地消除潜在的非上皮刺激物。 在23个MLR培养物中的18个中,常规辅助细胞去除的上皮细胞仍然能够刺激同种异体T淋巴细胞(S.I. = 5.5 [平均值];与单独的T细胞相比,P < 0.0005)。 在培养开始时添加抗II类单克隆抗体(VG2.2)完全抑制MLR反应(n = 10)。 在从气道上皮细胞MLR收集的淋巴细胞(1.42 +/-1.29)和从单独培养的T淋巴细胞(1.3 +/-0.75)的比率之间没有检测到CD 4 +/CD 8+比率的变化,表明CD+和CD 8 + T淋巴细胞都响应于气道上皮细胞上识别的同种抗原表位的刺激而增殖。 这些研究表明,气道上皮细胞可以刺激同种异体限制性T淋巴细胞,这种能力似乎与II类抗原的表达。 这一发现支持气道上皮细胞可能执行辅助细胞功能的假设,并且抗原的呈递可能不限于发现传统辅助细胞群的肺泡或间质室。
Expression of major histocompatibility complex (MHC) class II antigens is a requirement for accessory cell function in antigen presentation. Recent reports have demonstrated the presence of class II antigens on human bronchial epithelial cells. In the present study, immunohistochemical staining revealed HLA-DR on human airway epithelial cells obtained from two different mucosal sites (lobar bronchus and nasal turbinates). To determine whether airway epithelial cells bear functional class II molecules that allow for their cognate interaction with T lymphocytes, cells isolated from these sites were used in mixed lymphocyte cultures (MLR), as in vitro model of accessory cell function. Freshly isolated cells (11 bronchi/3 turbinates) stimulated allogeneic T lymphocytes (stimulation index [S.I.] = 9.3 [mean]; P < 0.001 compared to T cells alone). In order to assess the potential role of contaminating conventional accessory cells, bronchial epithelial cell isolates were first preincubated in a serum-free, growth factor-supplemented medium that functionally eliminates potential non-epithelial stimulators prior to MLR culture. Conventional accessory cell-depleted epithelial cells were still capable of stimulating allogeneic T lymphocytes in 18 of 23 MLR cultures (S.I. = 5.5 [mean]; P < 0.0005 compared to T cells alone). The addition of an anti-class II monoclonal antibody (VG2.2) at the onset of culture completely inhibited the MLR response (n = 10). No shift in the CD4+/CD8+ ratio was detected between lymphocytes harvested from airway epithelial cell MLR (1.42 +/- 1.29) and the ratio from T lymphocytes cultured alone (1.3 +/- 0.75), suggesting that both CD+ and CD8+ T lymphocytes were proliferating in response to stimulation from alloepitopes recognized on airway epithelial cells. These studies show that airway epithelial cells can stimulate allorestricted T lymphocytes, and that this capacity appears to be linked to class II antigen expression. This finding supports the hypothesis that airway epithelial cells may perform an accessory cell function, and that presentation of antigen may not be limited to the alveolar or interstitial compartments in which traditional accessory cell populations are found.