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. 1995 May;4(3):175–180. doi: 10.1155/S0962935195000287

Interleukin-2 receptor β chain as a possible target for low doses of mafosfamide

A Pukhalsky 1,✉, A Toptygina 1, S Khaidukov 2
PMCID: PMC2365629  PMID: 18475635

Abstract

The 7-day cytotoxic lymphocytes (CTL) induced in mixed lymphocyte culture express only the chain of the interleukin-2 receptor (IL-2R). In the present study this fact has been confirmed in a murine semi-allogeneic system. The ability of low doses of mafosfamide (Mf) to affect IL-2-induced CTL proliferation has been demonstrated. It was also shown that IL-2 activated resting suppressor cells. The pretreatment of the suppressor cells with either monoclonal antibodies (mAbs) against the p75 chain of IL-2R, or with Mf abolished the suppressive effect of these cells. No restoration of the proliferative response occurred when the anti-IL-2Rα mAb had been used. Flow cytometry analysis of 7-day CTL was carried out with mAbs against the α and β chains of IL-2R. CTL treatment with Mf inhibited anti-IL-2Rβ mAb binding. It may be assumed that the anti-proliferative effects of Mf which have been demonstrated in this paper, were a result of blocking the IL-2R β chain.

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Selected References

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  1. Bloemena E., Van Oers M. H., Weinreich S., Schellekens P. T. Cyclosporin A and prednisolone do not inhibit the expression of high-affinity receptors for interleukin 2. Clin Exp Immunol. 1988 Feb;71(2):308–313. [PMC free article] [PubMed] [Google Scholar]
  2. Diamantstein T., Willinger E., Reiman J. T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide. J Exp Med. 1979 Dec 1;150(6):1571–1576. doi: 10.1084/jem.150.6.1571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Hatakeyama M., Mori H., Doi T., Taniguchi T. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989 Dec 1;59(5):837–845. doi: 10.1016/0092-8674(89)90607-7. [DOI] [PubMed] [Google Scholar]
  4. Hatakeyama M., Tsudo M., Minamoto S., Kono T., Doi T., Miyata T., Miyasaka M., Taniguchi T. Interleukin-2 receptor beta chain gene: generation of three receptor forms by cloned human alpha and beta chain cDNA's. Science. 1989 May 5;244(4904):551–556. doi: 10.1126/science.2785715. [DOI] [PubMed] [Google Scholar]
  5. Hoover S. K., Barrett S. K., Turk T. M., Lee T. C., Bear H. D. Cyclophosphamide and abrogation of tumor-induced suppressor T cell activity. Cancer Immunol Immunother. 1990;31(2):121–127. doi: 10.1007/BF01742376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kiziroglu F., Miller R. G. Effect of cyclosporine on secondary cytotoxic T lymphocyte responses. Transplantation. 1990 May;49(5):961–965. doi: 10.1097/00007890-199005000-00024. [DOI] [PubMed] [Google Scholar]
  7. Leonard W. J., Depper J. M., Crabtree G. R., Rudikoff S., Pumphrey J., Robb R. J., Krönke M., Svetlik P. B., Peffer N. J., Waldmann T. A. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):626–631. doi: 10.1038/311626a0. [DOI] [PubMed] [Google Scholar]
  8. Nakamura Y., Russell S. M., Mess S. A., Friedmann M., Erdos M., Francois C., Jacques Y., Adelstein S., Leonard W. J. Heterodimerization of the IL-2 receptor beta- and gamma-chain cytoplasmic domains is required for signalling. Nature. 1994 May 26;369(6478):330–333. doi: 10.1038/369330a0. [DOI] [PubMed] [Google Scholar]
  9. Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):631–635. doi: 10.1038/311631a0. [DOI] [PubMed] [Google Scholar]
  10. Ohashi Y., Takeshita T., Nagata K., Mori S., Sugamura K. Differential expression of the IL-2 receptor subunits, p55 and p75 on various populations of primary peripheral blood mononuclear cells. J Immunol. 1989 Dec 1;143(11):3548–3555. [PubMed] [Google Scholar]
  11. Pukhal'skii A. L., Mezhneva A. P., Pevnitskii L. A. Chuvstvitel'nost' kletok selezenki myshei raznykh linii k antiproliferativnomu deistviiu alkiliruiushchikh soedinenii. Biull Eksp Biol Med. 1988 Feb;105(2):196–198. [PubMed] [Google Scholar]
  12. Pukhal'skii A. L., Toptygina A. P. Sravnitel'noe izuchenie mekhanizmov antiproliferativnogo deistviia nizkikh kontsentratsii mafosfamida i tsiklosporina a. Biull Eksp Biol Med. 1993 May;115(5):514–515. [PubMed] [Google Scholar]
  13. Pukhalsky A. L., Toptygina A. P., Viktorov V. V. Immunosuppressive action of cyclophosphamide in mice: contribution of some factors to determination of strain differences. Int J Immunopharmacol. 1993 May;15(4):509–514. doi: 10.1016/0192-0561(93)90065-7. [DOI] [PubMed] [Google Scholar]
  14. Reed J. C., Abidi A. H., Alpers J. D., Hoover R. G., Robb R. J., Nowell P. C. Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. J Immunol. 1986 Jul 1;137(1):150–154. [PubMed] [Google Scholar]
  15. Surya Y. A., Rosenfeld J. M., Hillcoat B. L. Cross-linking of DNA in L1210 cells and nuclei treated with cyclophosphamide and phosphoramide mustard. Cancer Treat Rep. 1978 Jan;62(1):23–29. [PubMed] [Google Scholar]
  16. Takeshita T., Asao H., Ohtani K., Ishii N., Kumaki S., Tanaka N., Munakata H., Nakamura M., Sugamura K. Cloning of the gamma chain of the human IL-2 receptor. Science. 1992 Jul 17;257(5068):379–382. doi: 10.1126/science.1631559. [DOI] [PubMed] [Google Scholar]
  17. Tanaka T., Tsudo M., Karasuyama H., Kitamura F., Kono T., Hatakeyama M., Taniguchi T., Miyasaka M. A novel monoclonal antibody against murine IL-2 receptor beta-chain. Characterization of receptor expression in normal lymphoid cells and EL-4 cells. J Immunol. 1991 Oct 1;147(7):2222–2228. [PubMed] [Google Scholar]
  18. Waldmann T. A. The IL-2/IL-2 receptor system: a target for rational immune intervention. Immunol Today. 1993 Jun;14(6):264–270. doi: 10.1016/0167-5699(93)90043-K. [DOI] [PubMed] [Google Scholar]

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