COUNTER-ANTIGEN PRESENTATION: FIBROBLASTS PRODUCE CYTOKINES BY SIGNALLING THROUGH HLA CLASS II MOLECULES WITHOUT INDUCING T-CELL PROLIFERATION

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2002-02, Vol.17 (4), p.175-181
• Main Authors: Ohyama, Hideki, Nishimura, Fusanori, Meguro, Michio, Takashiba, Shogo, Murayama, Yoji, Matsushita, Sho
• Format: Article
• Language: English
• Subjects: Antigen Presentation; Antigen-Presenting Cells - metabolism; Cells, Cultured; class II HLA/IL-6/IL-8/periodontal ligament fibroblasts/RANTES; Cytokines - biosynthesis; Fibroblasts - metabolism; HLA-DR Antigens - metabolism; Humans; Signal Transduction; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2001.0976

Fibroblasts are known to express histocompatibility leukocyte antigen DR (HLA-DR) molecules on their cell surface upon stimulation with interferon γ (IFN-γ), while the exact roles of HLA-DR on fibroblasts remain undetermined. To understand the role of HLA-DR molecules on fibroblasts, we examined whether: (1) fibroblasts act as antigen presenting cells (APC) which activate helper T (Th) cells; and/or (2) fibroblasts are activated via HLA-II molecules by making a T-cell receptor (TCR)–peptide–major histocompatibility complex (MHC) complex. We used Th0 clone HT8.3, which recognizes an antigenic peptide (Ag53 p141–161) in the context of DRB1*1501, as well as IFN-γ-treated and irradiated periodontal ligament fibroblasts (PDL) expressing DRB1*1501 molecules. When peptide-pulsed fibroblasts were co-incubated with HT8.3 treated by the protein synthesis inhibitor emetine, peptide-induced de novo expression of lymphokines and cell-surface molecules on T cells can be neglected. The antigen presenting capacity of these fibroblasts was evaluated by examining the proliferative responses of Th cells. Possible activation of fibroblasts by stimulation via HLA-DR molecules was evaluated by quantitating secreted cytokines in the supernatants after 18-h culture with or without anti-HLA-DR monoclonal antibody (mAb) or emetine-treated HT8.3. Indeed, Th cells did not show proliferative responses when peptide-pulsed PDL were used as APC, whereas PDL produced larger amounts of interleukin (IL) 6, IL-8, monocyte chemoattractant protein 1 (MCP-1) and regulated upon activation, normal T expressed and secreted (RANTES) compared with controls, when cultured with anti-HLA-DR mAb or emetine-treated HT8.3. These findings suggest that HLA-DR expressed on fibroblasts do not present antigens to induce T-cell proliferation, but may act as receptor molecules that transmit signals into fibroblasts, based on DR–peptide–TCR interaction, resulting in the secretion of several cytokine species.