Synthetic phosphoantigens enhance human Vgamma9Vdelta2 T lymphocytes killing of non-Hodgkin's B lymphoma.
BACKGROUND
Non-Hodgkin's B lymphomas (NHL) are often resistant to conventional treatments and, until now, immunotherapeutic approaches against NHL only aimed at inducing anti-tumor effectors. Nevertheless, human blood Vgamma9Vdelta2 T lymphocytes represent an abundant pool of cytotoxic tumor-reactive cells. Vgamma9Vdelta2 T cells are strongly activated by natural compounds, from which powerful synthetic ligands have been derived. These synthetic antigens induce efficient Vgamma9Vdelta2 T cell responses in vitro.


METHODS
We set up a series of Vgamma9Vdelta2 T cell-activation experiments, including cytotoxic activity and amplification from whole blood cells. Several types of Vgamma9Vdelta2 effectors were challenged against a panel of 16 B lymphoma cell lines. These tests have been performed in the absence and presence of -specific synthetic ligands to evaluate the effect of such molecules on anti-tumor activity.


RESULTS
We report here that Vgamma9Vdelta2 T cells recognize B lymphomas. This recognition is associated with the cytotoxic activity against B-lymphoma cells and/or proliferative responses, and appears to be T-cell antigen receptor (TCR)-dependent. Because few B lymphoma induce a complete set of Vgamma9Vdelta2 cell responses, a chemical ligand of Vgamma9Vdelta2 T cells was used to enhance both proliferation and cytotoxic activity of anti-B lymphoma effectors. We show that such synthetic compound improves Vgamma9Vdelta2 CTL numbers and lysis of B lymphoma lines, especially when the targets are already spontaneously recognized by these effectors.


CONCLUSIONS
We report here that human Vgamma9Vdelta2 T cells anti-B lymphoma response can be improved by use of specific synthetic ligands, which enhance their cytotoxic activity and allows their rapid expansion ex vivo.
Sicard
H
H
INSERM U395, Réponse Immunitaire et CMH, CHU Purpan, Toulouse, France. hsicard@purpan.inserm.fr
Al Saati
T
T
Delsol
G
G
Fournié
J J
JJ
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000473:pathology*; D010750:Phosphoproteins / Q000494:pharmacology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D008024:Ligands; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000099192:CD69 Antigens