Human Alveolar Epithelial Cells Type II are Capable of Regulating T-Cell Activity

Abstract

Alveolar epithelial cells type II (AEC-II) express MHC class II on their surface, an important prerequisite for antigen presentation. However, accessory signals are required for an efficient T-cell activation. We therefore isolated AEC-II from tumor-free sections of human lungs obtained by lobectomy/pneumectomy and purified the cells by magnetic-activated cell sorting. Furthermore, we tested the expression of CD54, CD58, CD80, and CD86 on AEC-II and evaluated their accessory function (AF) in cell culture using a coculture of interleukin-2 (IL-2), releasing Jurkat cells and AEC-II. An increased AF is documented by an elevated IL-2 release and expressed as accessory index (AI). In 33 experiments the AF of AEC-II proved to be highly variable. AI ranged between 0.3 and 17.1 with a median of 1.4 (0.3-17.1). Forty-four percent (4-77) of the AEC-II expressed HLA-DR, 44% (12-89%) of the cells expressed CD58, and CD54 was expressed by 55% (16-89%). AEC-II also expressed CD80 and CD86 (38% [0-77%] and 40% [4-68%), respectively). Interestingly, AEC-II released high levels of TGFβ (1730 pg/mL [771-5876]) and the accessory index could be increased (≈ 2-fold) by the addition of neutralizing anti-TGFβ antibodies or radiation. Thus, type II alveolar cells express costimulatory molecules and are able to deliver costimulatory signals for T cells, providing evidence that AEC-II are able to act as antigen-presenting and immunoregulatory cells of the lung. Additionally, the accessory function of AEC-II is under the control of endogenously released TGFβ.