Drug-induced expansion and differentiation of V gamma 9V delta 2 T cells in vivo: the role of exogenous IL-2

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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of immunology (1950) 2005-08, Vol.175 (3), p.1593-1598
Main Authors: Casetti, Rita, Perretta, Gemma, Taglioni, Alessandra, Mattei, Maurizio, Colizzi, Vittorio, Dieli, Francesco, D'Offizi, Gianpiero, Malkovsky, Miroslav, Poccia, Fabrizio
Format: Article
Language:English
Subjects:
2,3-Diphosphoglycerate - administration & dosage
2,3-Diphosphoglycerate - immunology
Algae
Animals
Antigens - administration & dosage
Antigens - immunology
Apicomplexa
Archaebacteria
CD4-CD8 Ratio
Cell Differentiation - drug effects
Cell Differentiation - immunology
Cell Proliferation - drug effects
Cells, Cultured
Cynomolgus
Diphosphates - administration & dosage
Diphosphates - immunology
Diphosphonates - administration & dosage
Diphosphonates - immunology
Epoxy Compounds - administration & dosage
Epoxy Compounds - immunology
Eubacteria
Hemiterpenes - administration & dosage
Hemiterpenes - immunology
Immunologic Memory - drug effects
Injections, Intravenous
Injections, Subcutaneous
Interferon-gamma - biosynthesis
Interleukin-2 - administration & dosage
Interleukin-2 - physiology
Macaca fascicularis
Organophosphorus Compounds - administration & dosage
Organophosphorus Compounds - immunology
Pamidronate
Receptors, Antigen, T-Cell, gamma-delta - physiology
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - drug effects
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Th1 Cells - cytology
Th1 Cells - drug effects
Th1 Cells - immunology
Th1 Cells - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.175.3.1593