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Histamine modulates γδ-T lymphocyte migration and cytotoxicity, via Gi and Gs protein-coupled signalling pathways
K Truta-Feles1, M Lagadari, K Lehmann
1Department of Dermatology, Friedrich Schiller University of Jena, Jena, Germany.
Background And Purpose:
The biogenic amine, histamine plays a pathophysiological regulatory role in cellular processes of a variety of immune cells. This work analyses the actions of histamine on γδ-T lymphocytes, isolated from human peripheral blood, which are critically involved in immunological surveillance of tumours.
Experimental Approach:
We have analysed effects of histamine on the intracellular calcium, actin reorganization, migratory response and the interaction of human γδ T cells with tumour cells such as the A2058 human melanoma cell line, the human Burkitt's Non-Hodgkin lymphoma cell line Raji, the T-lymphoblastic lymphoma cell line Jurkat and the natural killer cell-sensitive erythroleukaemia cell line, K562.
Key Results:
γδ T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood γδ T cells, histamine stimulated Pertussis toxin-sensitive intracellular calcium increase, actin polymerization and chemotaxis. However, histamine inhibited the spontaneous cytolytic activity of γδ T cells towards several tumour cell lines in a cholera toxin-sensitive manner. A histamine H(4) receptor antagonist abolished the histamine induced γδ T cell migratory response. A histamine H(2) receptor agonist inhibited γδ T cell-mediated cytotoxicity.
Conclusions And Implications:
Histamine activated signalling pathways typical of chemotaxis (G(i) protein-dependent actin reorganization, increase of intracellular calcium) and induced migratory responses in γδ T lymphocytes, via the H(4) receptor, whereas it down-regulated γδ T cell mediated cytotoxicity through H(2) receptors and G(s) protein-coupled signalling. Our data suggest that histamine activated γδ T cells could modulate immunological surveillance of tumour tissue.
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