Expression of class II major histocompatibility complex antigens on alveolar epithelium in interstitial lung disease: relevance to pathogenesis of idiopathic pulmonary fibrosis.

Abstract

To determine whether expression of class II major histocompatibility complex antigens on alveolar epithelium is relevant to the pathogenesis of idiopathic pulmonary fibrosis (IPF) lung biopsy specimens were investigated from nine patients with IPF with or without connective tissue disease, four patients with sarcoidosis, eight patients with lung disease of presumably infectious origin, and five controls. The alveolar epithelium stained strongly with anti-Ia (HLA-DR) or Leu 10 (HLA-DS) monoclonal antibodies, in eight of nine biopsy specimens from patients with IPF, in three of four biopsy specimens from patients with sarcoidosis, in all six biopsy specimens from patients with presumably viral, mycobacterial, or pneumocystic lung disease, but not in control lung tissue, nor in two biopsy specimens from patients with bacterial pneumonia. Mononuclear cell infiltrates consisted of T4 positive (helper/inducer) lymphocytes, predominantly present in a nodular arrangement in the interstitium, and T8 positive (cytotoxic/suppressor) cells, distributed equally in the interstitium and subepithelially or intraepithelially. T8 cells outnumbered T4 cells in six of nine biopsy specimens from patients with IPF, but in none of the biopsy specimens from patients with sarcoidosis or interstitial lung disease of infectious origin. Although the expression of class II antigens on the alveolar epithelium which is infiltrated by T8 cells in IPF is consistent with local presentation of autoantigens and an ensuing local immune response, class II expression is also present in interstitial lung disease of sarcoidosis and microbial infections: its role in the pathogenesis of IPF must therefore remain speculative.

Major histocompatibility complex and alveolar epithelial apoptosis in idiopathic pulmonary fibrosis

“…Importantly, the expression of MHC class II molecules is actively regulated upon various cellular stimuli, and it has been demonstrated that alveolar epithelial cells from IPF lungs express HLA class II molecules (Kallenberg et al 1987). Moreover, some experimental work has shown that class II MHC antigens is expressed early on the type II alveolar epithelium and before any inflammatory cellular infiltration (Nakayama et al 1992).…”

Primary type II alveolar epithelial cells present microbial antigens to antigen-specific CD4+T cells

“…Although human and rat type II AEC express class II major histocompatibility complex (MHC) antigens on their cell surface, their role as antigen presenting cells has never been directly addressed (11,12,19,21). We hypothesize that type II AEC may function as antigen-presenting cells (APC) during pulmonary infection.…”

Pneumocystis carinii Cell Wall β-Glucan Induces Release of Macrophage Inflammatory Protein-2 from Alveolar Epithelial Cells via a Lactosylceramide-mediated Mechanism

“…However, accumulating evidence demonstrates that pulmonary alveolar epithelial cells not only function as a passive barrier mediating gas exchange but also actively participate in the host immune response. Alveolar epithelial cells are capable of processing and presenting antigen to T lymphocytes (18,19). Furthermore, isolated alveolar epithelial cells produce and secrete various cytokines and chemokines, including TNF␣ and MIP-2, when stimulated with bacterial components like li-popolysaccharide (LPS) or whole organisms such as Mycobacterium tuberculosis (20 -23).…”