On the role of co-inhibitory molecules in dendritic cell: T helper cell coculture assays aimed to detect chemical-induced contact allergy

Exp Suppl. 2014:104:115-35. doi: 10.1007/978-3-0348-0726-5_9.

Abstract

T cells play a pivotal role in sensitization and elicitation of type IV allergic reactions. While T helper cells sustain and maintain the differentiation of further effector cells, regulatory T cells are involved in control of cytokine release and proliferation, and T killer cells execute cellular lysis, thereby leading to certain levels of tissue damage. According to their central role, the widely applied and OECD-supported test method for the assessment of the sensitization potential of a chemical, i.e., the local lymph node assay (LLNA), relies on the detection of the immune-responsive proliferation of lymphocytes. However, most sensitization assays recently developed take advantage of the initiators of sensitization, dendritic cells (DCs) or DC-like cell lines. Here, we focus on inhibitory molecules expressed on the surface of DCs and their corresponding receptors on T cells. We summarize insight into the function of CTLA-4, the ligands of inducible co-stimulators (ICOSs), and on the inhibitory receptor programmed death (PD). The targeting of immune cell surface receptors by inhibitory molecules holds some promise with regard to the development of T cell-based sensitization assays. Firstly, a broader and more sensitive dynamic range of detection could be achieved by blocking inhibitors or by removing inhibiting regulatory T cells from the assays. Secondly, the actual expression levels of inhibitory molecules could be also a valuable indicator for the process of sensitization. Finally, inhibitory molecules in coculture test systems are supposed to have a major influence on DCs by reverse signaling, thereby affecting their differentiation and maturation status in a feedback loop. In conclusion, inhibitory ligands of DC surface receptors and/or their cognate receptors on T cells could serve as useful tools in cell-based assays, directly influencing toxicological endpoints such as sensitization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allergens / immunology*
  • Allergens / toxicity
  • Animals
  • Coculture Techniques
  • Costimulatory and Inhibitory T-Cell Receptors / immunology
  • Costimulatory and Inhibitory T-Cell Receptors / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dermatitis, Contact / etiology
  • Dermatitis, Contact / immunology*
  • Haptens / immunology*
  • Haptens / toxicity
  • Humans
  • Immunologic Techniques
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism

Substances

  • Allergens
  • Costimulatory and Inhibitory T-Cell Receptors
  • Haptens
  • Receptors, Antigen, T-Cell