Phenotype and functional changes of Vgamma9/Vdelta2 T lymphocytes in Behçet's disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity.
BACKGROUND
Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-alpha) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vgamma9/Vdelta2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vgamma9/Vdelta2 T cell expansion, activation and cytotoxicity.


METHODS
We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vgamma9/Vdelta2 T lymphocytes by means of fluorescence-activated cell sorter analysis of lymphocyte cultures from patients with active and inactive BD and healthy subjects.


RESULTS
Cell expansion, expression of TNFRII, perforin and gamma IFN content and release of granzyme A were significantly higher in active patients. In vitro and ex vivo treatment with infliximab resulted in a significant reduction of all parameters together with changes in the phenotype of Vgamma9/Vdelta2 T cells.


CONCLUSIONS
All together these data indicate that infliximab is capable of interfering with Vgamma9/Vdelta2 T cell function in BD and although cell culture models cannot reliably predict all potential effects of the drug in vivo, our results present the possibility that this drug may find use in a range of immunological disorders, characterized by dysregulated cell-mediated immunity.
Department of Internal Medicine, Division of Rheumatology, University of Palermo, piazza delle Cliniche 2, 90127 Palermo, Italy.
Antonina
A
Accardo-Palumbo
Anna Rita
AR
Giardina
Francesco
F
Ciccia
Angelo
A
Ferrante
Alfonso
A
Principato
Rosalia
R
Impastato
Ennio
E
Giardina
Giovanni
G
Triolo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology; D001528:Behcet Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D000069285:Infliximab; D007371:Interferon-gamma / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin / Q000378:metabolism; D010641:Phenotype; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D016692:Receptors, Antigen, T-Cell, gamma-delta; D047889:Receptors, Tumor Necrosis Factor, Type II; D054353:Perforin; D007371:Interferon-gamma; D000069285:Infliximab; D053804:Granzymes