Human Vgamma9Vdelta2 T cells recognize nonpeptidic Ags generated by the 1-deoxy-d-xylulose 5-phosphate (many eubacteria, algae, plants, and Apicomplexa) and mevalonate (eukaryotes, archaebacteria, and certain eubacteria) pathways of isoprenoid synthesis. The potent Vgamma9Vdelta2 T cell reactivity 1) against certain cancer cells or 2) induced by infectious agents indicates that therapeutic augmentations of Vgamma9Vdelta2 T cell activities may be clinically beneficial. The functional characteristics of Vgamma9Vdelta2 T cells from Macaca fascicularis (cynomolgus monkey) are very similar to those from Homo sapiens. We have found that the i.v. administration of nitrogen-containing bisphosphonate or pyrophosphomonoester drugs into cynomolgus monkeys combined with s.c. low-dose (6 x 10(5) U/animal) IL-2 induces a large pool of CD27+ and CD27- effector/memory T cells in the peripheral blood of treated animals. The administration of these drugs in the absence of IL-2 is substantially less effective, indicating the importance of additional exogenous costimuli. Shortly after the costimulatory IL-2 treatment, only gammadelta (but not alphabeta) T cells expressed the CD69 activation marker, indicating that Vgamma9Vdelta2 T lymphocytes are more responsive to low-dose IL-2 than alphabeta T cells. Up to 100-fold increases in the numbers of peripheral blood Vgamma9Vdelta2 T cells were observed in animals receiving the gammadelta stimulatory drug plus IL-2. Moreover, the expanded Vgamma9Vdelta2 T cells were potent Th1 effectors capable of releasing large amounts of IFN-gamma. These results may be relevant for designing novel (or modifying current) immunotherapeutic trials with nitrogen-containing bisphosphonate or pyrophosphomonoester drugs.
|Data di pubblicazione:||2005|
|Titolo:||Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2|
|Autori:||CASETTI R; PERRETTA G; TAGLIONI A; MATTEI M; COLIZZI V; DIELI F; D'OFFIZI G; MALKOVSKY M; POCCIA F|
|Tipologia:||Articolo su rivista|
|Citazione:||CASETTI R, PERRETTA G, TAGLIONI A, MATTEI M, COLIZZI V, DIELI F, et al. (2005). Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2. JOURNAL OF IMMUNOLOGY, 175, 1593-1598.|
|Appare nelle tipologie:||01 - Articolo su rivista|