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9V
2 T Cells In Vivo: The Role of Exogenous IL-21
* National Institute for Infectious Diseases, "Lazzaro Spallanzani," Istituto di Ricerca e Cura a Carattere Scientifico, Rome, Italy; Institute of Neurobiology and Molecular Medicine, Consiglio Nazionale delle Ricerche, Rome, Italy; Department of Biology, University of Rome "Tor Vergata," Rome, Italy; Department of Biopathology, University of Palermo, Palermo, Italy; and ¶ University of Wisconsin Medical School, Madison, WI 53706.
Human V
9V
2 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 V9V2 T cell reactivity 1) against certain cancer cells or 2) induced by infectious agents indicates that therapeutic augmentations of V9V2 T cell activities may be clinically beneficial. The functional characteristics of V9V2 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 105 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 (but not 
) T cells expressed the CD69 activation marker, indicating that V9V2 T lymphocytes are more responsive to low-dose IL-2 than T cells. Up to 100-fold increases in the numbers of peripheral blood V9V2 T cells were observed in animals receiving the stimulatory drug plus IL-2. Moreover, the expanded V9V2 T cells were potent Th1 effectors capable of releasing large amounts of IFN-. These results may be relevant for designing novel (or modifying current) immunotherapeutic trials with nitrogen-containing bisphosphonate or pyrophosphomonoester drugs.
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