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Histamine influences T-cell reactions via histamine receptors 1 and 2. The histamine receptor 4 (H₄R) is the most recently identified histamine receptor and is also expressed on human CD4⁺ T cells; however, its regulation and function are unclear.

To investigate expression, regulation, and function of the H₄R on human CD4⁺ T cells.

Histamine receptor 4 expression was studied by real-time quantitative RT-PCR and by flow cytometry. Effects of H₄R stimulation on induction of the signal transduction molecules activator protein 1 (AP-1) and nuclear factor-κB (NF-κB) were determined by electrophoretic mobility shift assay and on cytokine production by RT-PCR and ELISA.

Histamine receptor 4 mRNA and protein were expressed by CD4⁺ T cells and upregulated by IL-4. Its expression was higher on T_H2 cells than T_H1 cells and naive T-cells. H₄R agonists …