Zambello R, Trentin L, Benetti R, Cipriani A, Crivellaro C, Cadrobbi P, Agostini C, Semenzato G
Padua University School of Medicine, Department of Clinical Medicine, Padua Hospital, Italy.
J Clin Immunol. 1992 Sep;12(5):371-80. doi: 10.1007/BF00920795.
Lung involvement in patients affected by HIV-1 infection is characterized by an alveolitis sustained by the accumulation of CD8+ T lymphocytes. To investigate whether in situ T cell growth plays a relevant role in the pooling of CD8+ lymphocytes, we have analyzed the activity of two lymphokines involved in the mechanisms of T cell proliferation, i.e., interleukin-2 (IL-2) and interleukin-4. To this aim, following appropriate triggering and blocking, the expression and the functional role of IL-2 receptors (IL-2R) (both p55 and p75 chains) and IL-4 receptors have been analyzed on T lymphocytes obtained from the bronchoalveolar lavage (BAL) of 16 HIV-1+ patients. Molecular and phenotypic studies we performed demonstrated that CD8+ lymphocytes from the BAL of HIV-1 + patients strongly expressed the p75 chain of IL-2 receptor, while neither p55 mRNA nor its surface membrane product (Tac antigen) was detectable; in addition, there was no expression of IL-4 receptors. IL-2 stimulation was able to induce T cell growth in a dose-dependent manner, whereas IL-4 did not. Finally, using mAbs which specifically block the p55 or p75 IL-2R, we showed that both subunits of IL-2R were involved in the proliferative activity of lung lymphocytes. The results obtained in the present study directly demonstrate that BAL T lymphocytes of HIV-1 + patients express a fully functional IL-2 receptor apparatus, pointing to the role for this lymphokine in maintaining the alveolitis taking place in the lungs of AIDS patients.
HIV-1感染患者的肺部受累表现为CD8+ T淋巴细胞积聚导致的肺泡炎。为了研究原位T细胞生长在CD8+淋巴细胞聚集过程中是否起相关作用,我们分析了参与T细胞增殖机制的两种淋巴细胞因子,即白细胞介素-2(IL-2)和白细胞介素-4的活性。为此,在进行适当的触发和阻断后,对从16例HIV-1阳性患者的支气管肺泡灌洗(BAL)中获得的T淋巴细胞上IL-2受体(IL-2R)(p55和p75链)和IL-4受体的表达及功能作用进行了分析。我们进行的分子和表型研究表明,HIV-1阳性患者BAL中的CD8+淋巴细胞强烈表达IL-2受体的p75链,而未检测到p55 mRNA及其表面膜产物(Tac抗原);此外,也没有IL-4受体的表达。IL-2刺激能够以剂量依赖的方式诱导T细胞生长,而IL-4则不能。最后,使用特异性阻断p55或p75 IL-2R的单克隆抗体,我们表明IL-2R的两个亚基均参与肺淋巴细胞的增殖活性。本研究获得的结果直接证明,HIV-1阳性患者的BAL T淋巴细胞表达功能完整的IL-2受体装置,表明该淋巴细胞因子在维持艾滋病患者肺部发生的肺泡炎中发挥作用。