Experimental hypersensitivity pneumonitis: in vitro effects of interleukin-2 and interferon-gamma.

R Fei, K Gott, B Edwards, M Schuyler
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Abstract

Cultured CD4+ cells are responsible for transfer of adoptive murine experimental hypersensitivity pneumonitis (EHP) (ARRD 1992; 146:1582-8). To characterize interactions that occur in vitro that result in cells able to transfer EHP, we added either antibody to IFN-gamma, antibody to IL-2, or 30 or 300 micrograms/ml IFN-gamma at the onset of 72-hour culture of C3H/HeJ spleen cells from either M. faeni or ovalbumin (control) sensitized donors with 30 micrograms/ml Micropolyspora faeni. We determined the phenotype of cells after culture and the amount of IL-2 or IFN-gamma in the culture supernatants, transferred cells to naive recipients, challenged the recipients intratracheally with M. faeni, and determined the extent of pulmonary inflammatory changes 4 days thereafter. Substantial amounts of IL-2 and IFN-gamma were detected in supernatants of cultures from M. faeni-sensitized animals, and lesser amounts were detected in culture supernatants from ovalbumin-sensitized donors. Treatment of cultures of M. faeni-sensitized cells with antibody to IL-2 or IFN-gamma blocked or reduced measurable IL-2 or IFN-gamma for the duration of culture. Treatment with IFN-gamma blocked increased levels of IL-2 at 48 and 72 hours of culture. Cultured M. faeni-sensitized cells adoptively transfer EHP. Cells from cultures depleted of either IL-2 or IFN-gamma or supplemented with IFN-gamma could transfer EHP equally well. We conclude that in vitro maturation of cells capable of adoptive EHP is not dependent on soluble IL-2 or IFN-gamma and is not altered by exogenous IFN-gamma.

实验性超敏性肺炎:白细胞介素-2和干扰素γ的体外作用。
培养的CD4+细胞负责过继性小鼠实验性过敏性肺炎(EHP)的转移(ARRD 1992;146:1582-8)。为了表征体外发生的导致细胞能够转移EHP的相互作用,我们在C3H/HeJ脾细胞培养72小时开始时添加ifn - γ抗体、IL-2抗体或30或300微克/毫升ifn - γ,这些细胞来自faeni微多孢子虫或卵清蛋白(对照)致敏的供者,并添加30微克/毫升faeni微多孢子虫。我们测定了培养后细胞的表型和培养上清液中IL-2或ifn - γ的含量,将细胞转移到初始受体,气管内用M. faeni攻击受体,并在4天后测定肺部炎症变化的程度。在faeni致敏动物的培养上清液中检测到大量的IL-2和ifn - γ,而在卵清蛋白致敏供体的培养上清液中检测到较少的IL-2和ifn - γ。用IL-2或ifn - γ抗体处理faeni致敏细胞的培养物,在培养期间阻断或降低可测量的IL-2或ifn - γ。ifn - γ治疗阻断了培养48和72小时时IL-2水平的升高。培养的faeni致敏细胞过继性转移EHP。无论是缺乏IL-2还是ifn - γ,或者补充ifn - γ,培养的细胞都能很好地转移EHP。我们得出结论,能够过继性EHP的细胞的体外成熟不依赖于可溶性IL-2或ifn - γ,也不受外源性ifn - γ的改变。
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