Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2

Francesco Dieli, Gianpiero D'Offizi, Maurizio Mattei, Rita Casetti, Alessandra Taglioni, Gemma Perretta, Vittorio Colizzi, Miroslav Malkovsky, Fabrizio Poccia

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Abstract

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.
Original languageEnglish
Pages (from-to)1593-1598
JournalJournal of Immunology
Volume175
Publication statusPublished - 2005

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Dieli, F., D'Offizi, G., Mattei, M., Casetti, R., Taglioni, A., Perretta, G., Colizzi, V., Malkovsky, M., & Poccia, F. (2005). Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2. Journal of Immunology, 175, 1593-1598.