Counter-antigen presentation: Fibroblasts produce cytokines by signalling through HLA class II molecules without inducing T-cell proliferation

Hideki Ohyama, Fusanori Nishimura, Michio Meguro, Shogo Takashiba, Yoji Murayama, Sho Matsushita

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)175-181
Number of pages7
JournalCytokine
Volume17
Issue number4
DOIs
Publication statusPublished - 2002

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Keywords

  • Class II HLA
  • IL-6
  • IL-8
  • Periodontal ligament fibroblasts
  • RANTES

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

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