Histamine modulates γδ-T lymphocyte migration and cytotoxicity, via Gi and Gs protein-coupled signalling pathways

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 gamma delta-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 gamma delta 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: gamma delta T lymphocytes express mRNA for different histamine receptor subtypes. In human peripheral blood gamma delta T cells, histamine stimulated Pertussis toxin-sensitive intracellular calcium increase, actin polymerization and chemotaxis. However, histamine inhibited the spontaneous cytolytic activity of gamma delta T cells towards several tumour cell lines in a cholera toxin-sensitive manner. A histamine H-4 receptor antagonist abolished the histamine induced gamma delta T cell migratory response. A histamine H-2 receptor agonist inhibited gamma delta 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 gamma delta T lymphocytes, via the H-4 receptor, whereas it down-regulated gamma delta T cell mediated cytotoxicity through H-2 receptors and G(s) protein-coupled signalling. Our data suggest that histamine activated gamma delta T cells could modulate immunological surveillance of tumour tissue.