Schuyler Mark, Gott Katherine, Cherne Amy
Department of Medicine, Albuquerque VA Medical Center, University of New Mexico School of Medicine, Albuquerque, NM 87108, USA.
Int J Exp Pathol. 2002 Apr;83(2):87-98. doi: 10.1046/j.1365-2613.2002.00217.x.
Inhalation of Saccharopolyspora rectivirgula (SR) can cause the disease Farmer's Lung, a classic example of hypersensitivity pneumonitis. Th1, but not Th2, cell lines can adoptively transfer experimental hypersensitivity pneumonitis (EHP). Substantial amounts of IL12 appear in bronchoalveolar lavage fluid (BALF) after a single intratracheal (IT) injection of SR, and SR-induced IL12 secretion by both a macrophage cell line and alveolar macrophages. We tested the hypothesis that IL12 is essential for the development of EHP by addition of anti-IL12 to cultured cells, and adoptive transfer of EHP in IL12p40-/- animals. We transferred SR cultured spleen and lung associated lymph node cells from SR sensitized mice (both IL12p40-/- and wild type), to naïve recipients (both wild type and IL12p40-/-). The addition of anti-IL12 to cultures of sensitized cells could not ablate the ability of these cells to transfer EHP. Cultured cells from IL12p40-/- animals were fully capable of transferring EHP. In contrast, IL12p40-/- recipients of both wild type and IL12p40-/--cultured cells were less able to express EHP (lung histology and BALF characteristics) than wild type mice, and had more eosinophils in both lung tissue and BALF. We conclude that IL12 is not necessary for development of cells able to adoptively transfer EHP, but that it is required for full expression of EHP in recipient animals.
吸入直丝链孢菌(SR)可引发农民肺疾病,这是超敏性肺炎的一个典型例子。Th1细胞系而非Th2细胞系能够过继转移实验性超敏性肺炎(EHP)。单次气管内注射SR后,支气管肺泡灌洗液(BALF)中会出现大量白细胞介素12(IL12),并且巨噬细胞系和肺泡巨噬细胞均可由SR诱导分泌IL12。我们通过向培养细胞中添加抗IL12以及在IL12p40基因敲除动物中过继转移EHP,来检验IL12对EHP发展至关重要这一假说。我们将来自经SR致敏的小鼠(包括IL12p40基因敲除小鼠和野生型小鼠)的培养脾脏及肺相关淋巴结细胞,转移至未致敏的受体(包括野生型小鼠和IL12p40基因敲除小鼠)。向致敏细胞培养物中添加抗IL12并不能消除这些细胞过继转移EHP的能力。来自IL12p40基因敲除动物的培养细胞完全能够过继转移EHP。相比之下,野生型和IL12p40基因敲除小鼠培养细胞的IL12p40基因敲除受体表达EHP(肺组织学和BALF特征)的能力低于野生型小鼠,并且在肺组织和BALF中嗜酸性粒细胞更多。我们得出结论,IL12对于能够过继转移EHP的细胞的发育并非必需,但对于受体动物中EHP的充分表达却是必需的。