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.
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Abbreviations
- ACD:
-
Allergic contact dermatitis
- CTLA-4:
-
Cytotoxic lymphocyte-associated antigen-4
- DC:
-
Dendritic cell
- DNCB:
-
2,4-Dinitrochlorobenzene
- DNFB:
-
2,4-Dinitrofluorobenzene
- ICOS:
-
Inducible co-stimulator
- LC:
-
Langerhans cell
- LLNA:
-
Local lymph node assay
- MoDC:
-
Monocyte-derived DC
- PBMC:
-
Peripheral blood mononuclear cell
- PD:
-
Programmed death
- Th:
-
T helper
- Treg :
-
Regulatory T cell
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Acknowledgment
This work was supported by intramural grant SFP1322-345 and the German Federal Ministry of Education and Research (BMBF), project #0315724.
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Peiser, M., Hitzler, M., Luch, A. (2014). On the Role of Co-inhibitory Molecules in Dendritic Cell: T Helper Cell Coculture Assays Aimed to Detect Chemical-Induced Contact Allergy. In: Martin, S. (eds) T Lymphocytes as Tools in Diagnostics and Immunotoxicology. Experientia Supplementum, vol 104. Springer, Basel. https://doi.org/10.1007/978-3-0348-0726-5_9
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