PMID- 24214622
OWN - NLM
STAT- MEDLINE
DCOM- 20140130
LR  - 20181206
IS  - 1664-431X (Print)
IS  - 1664-431X (Linking)
VI  - 104
DP  - 2014
TI  - On the role of co-inhibitory molecules in dendritic cell: T helper cell coculture 
      assays aimed to detect chemical-induced contact allergy.
PG  - 115-35
LID - 10.1007/978-3-0348-0726-5_9 [doi]
AB  - 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.
FAU - Peiser, Matthias
AU  - Peiser M
AD  - Department of Product Safety, German Federal Institute for Risk Assessment (BfR), 
      Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany, Matthias.Peiser@bfr.bund.de.
FAU - Hitzler, Manuel
AU  - Hitzler M
FAU - Luch, Andreas
AU  - Luch A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - Switzerland
TA  - Exp Suppl
JT  - Experientia supplementum (2012)
JID - 101738007
RN  - 0 (Allergens)
RN  - 0 (Costimulatory and Inhibitory T-Cell Receptors)
RN  - 0 (Haptens)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Allergens/*immunology/toxicity
MH  - Animals
MH  - Coculture Techniques
MH  - Costimulatory and Inhibitory T-Cell Receptors/immunology/*metabolism
MH  - Dendritic Cells/immunology/*metabolism
MH  - Dermatitis, Contact/etiology/*immunology
MH  - Haptens/*immunology/toxicity
MH  - Humans
MH  - Immunologic Techniques
MH  - Receptors, Antigen, T-Cell/immunology/metabolism
MH  - T-Lymphocytes, Helper-Inducer/*immunology/metabolism
EDAT- 2013/11/12 06:00
MHDA- 2014/01/31 06:00
CRDT- 2013/11/12 06:00
PHST- 2013/11/12 06:00 [entrez]
PHST- 2013/11/12 06:00 [pubmed]
PHST- 2014/01/31 06:00 [medline]
AID - 10.1007/978-3-0348-0726-5_9 [doi]
PST - ppublish
SO  - Exp Suppl. 2014;104:115-35. doi: 10.1007/978-3-0348-0726-5_9.