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


METHODS
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.


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
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.
Department of Dermatology, Friedrich Schiller University of Jena, Jena, Germany.
K
K
Truta-Feles
M
M
Lagadari
K
K
Lehmann
L
L
Berod
S
S
Cubillos
S
S
Piehler
Y
Y
Herouy
D
D
Barz
T
T
Kamradt
Aa
A
Maghazachi
J
J
Norgauer
D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000502:physiology*; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
D016692:Receptors, Antigen, T-Cell, gamma-delta; D011968:Receptors, Histamine; D006632:Histamine; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs