Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A

K. Nomoto, M. Eto, K. Yanaga, Y. Nishimura, T. Maeda, K. Nomoto

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Abstract

In a murine strain combination identical in H-2 Ag but disparate in minor histocompatibility (H) Ag consisting of C3H/He (C3H; H-2(k), Mls-1b) mice as recipients and AKR/J (AKR; H-2(k), Mls-1a) mice as donors, a permanent skin allograft tolerance can be achieved by the cyclophosphamide (CP)-induced tolerance system that consists of i.v. injection of donor spleen cells (day- 2) and i.p. injection of CP 2 days later (day 0). Such permanent take of allografts in CP-induced tolerant mice was interfered with by intramuscular injection of cyclosporin A (CsA) from day -5 to day -1 and their grafts were rejected by 21 days after grafting. Mls-1a-reactive CD4+Vβ6+ T cells in the periphery, as the indicator to follow the kinetics of donor-reactive T cells, increased on day 0 and day 3 in the C3H mice treated with AKR spleen cells alone, whereas they disappeared rapidly from day 0 to day 3 in CP- induced tolerant mice. When CsA capable of interfering with IL-2 production and T cell proliferation was administered before CP treatment in CP-induced tolerance system, the number of CD4+Vβ6+ T cells in periphery did not increase on day 0 and 3, but increased on day 7 in contrast to the decreased number of those in CP-induced tolerant mice. On day 7, MLR against donor cells was decreased in CP-induced tolerant mice, but maintained in CsA- interfered tolerant mice. These result may indicate that the destruction of donor-Ag-stimulated, proliferating T cells by CP is interfered with by CsA, probably because CsA inhibits the proliferation of donor-reactive T cells at the time of CP treatment. Furthermore, these results also implicate that the protocol for immunosuppression with CsA and antimetabolites has to be designed carefully in clinical transplantation.

Original languageEnglish
Pages (from-to)2668-2674
Number of pages7
JournalJournal of Immunology
Volume149
Issue number8
Publication statusPublished - Jan 1 1992

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Nomoto, K., Eto, M., Yanaga, K., Nishimura, Y., Maeda, T., & Nomoto, K. (1992). Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A. Journal of Immunology, 149(8), 2668-2674.