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

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

Risultato della ricerca: Article

68 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)1593-1598
RivistaJournal of Immunology
Volume175
Stato di pubblicazionePublished - 2005

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Interleukin-2
T-Lymphocytes
Pharmaceutical Preparations
Macaca fascicularis
Diphosphonates
Nitrogen
Apicomplexa
Bacteria
Mevalonic Acid
Archaea
Terpenes
Eukaryota

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cita questo

Dieli, F., Casetti, R., Taglioni, A., Perretta, G., Colizzi, V., Malkovsky, M., ... Mattei, M. (2005). Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2. Journal of Immunology, 175, 1593-1598.

Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2. / Dieli, Francesco; Casetti, Rita; Taglioni, Alessandra; Perretta, Gemma; Colizzi, Vittorio; Malkovsky, Miroslav; Poccia, Fabrizio; D'Offizi, Gianpiero; Mattei, Maurizio.

In: Journal of Immunology, Vol. 175, 2005, pag. 1593-1598.

Risultato della ricerca: Article

Dieli, F, Casetti, R, Taglioni, A, Perretta, G, Colizzi, V, Malkovsky, M, Poccia, F, D'Offizi, G & Mattei, M 2005, 'Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2', Journal of Immunology, vol. 175, pagg. 1593-1598.
Dieli F, Casetti R, Taglioni A, Perretta G, Colizzi V, Malkovsky M e altri. Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2. Journal of Immunology. 2005;175:1593-1598.
Dieli, Francesco ; Casetti, Rita ; Taglioni, Alessandra ; Perretta, Gemma ; Colizzi, Vittorio ; Malkovsky, Miroslav ; Poccia, Fabrizio ; D'Offizi, Gianpiero ; Mattei, Maurizio. / Drug-induced expansion and differentiation of Vg9Vd2 T cells in vivo: the role of exogenous IL-2. In: Journal of Immunology. 2005 ; Vol. 175. pagg. 1593-1598.
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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.",
author = "Francesco Dieli and Rita Casetti and Alessandra Taglioni and Gemma Perretta and Vittorio Colizzi and Miroslav Malkovsky and Fabrizio Poccia and Gianpiero D'Offizi and Maurizio Mattei",
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AU - Dieli, Francesco

AU - Casetti, Rita

AU - Taglioni, Alessandra

AU - Perretta, Gemma

AU - Colizzi, Vittorio

AU - Malkovsky, Miroslav

AU - Poccia, Fabrizio

AU - D'Offizi, Gianpiero

AU - Mattei, Maurizio

PY - 2005

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N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/22081

M3 - Article

VL - 175

SP - 1593

EP - 1598

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

ER -