DONOR-SPECIFIC PROLONGATION OF RAT SKIN GRAFT SURVIVAL INDUCED BY RAT-DONOR CELLS AND CYCLOPHOSPHAMIDE UNDER COADMINISTRATION OF MONOCLONAL ANTIBODIES AGAINST T CELL RECEPTOR ???? AND NATURAL KILLER CELLS IN MICE1
1996; Wolters Kluwer; Volume: 61; Issue: 1 Linguagem: Inglês
10.1097/00007890-199601150-00023
ISSN1534-6080
AutoresMasayoshi Umesue, Hisanori Mayumi, Yousuke Nishimura, Young–Yun Kong, Kazuya Omoto, Yoshiyuki Murakami, Kikuo Nomoto,
Tópico(s)Immunotherapy and Immune Responses
ResumoBecause of the recent interest in human xenotransplantation, we investigated the possibility of inducing tolerance in a xenogeneic combination using cyclophosphamide (CP). Donor-specific prolongation of xenogeneic Fisher 344 (F344) rat skin graft survival for up to 60 days was induced in C57BL/6(B6) mice by giving F344 bone marrow cells and spleen cells on day 0, CP on day 2, and monoclonal antibodies against murine TCR-αβ and NK1.1 on days -1 and 3. The inoculation of the xenogeneic cells brought accelerated repopulation of TCR-αβ+ T cells, even under the administration of anti-TCR-αβ mAb. The quick increase of the host TCR-αβ+ T cells caused by the xenogeneic cell injection was deeply suppressed by CP. Mixed lymphocyte reaction, CTL activity, and antibody production against donor F344 were profoundly suppressed for 50 days. Mixed xenogeneic chimerism was observed for 1 month after the inoculation of donor cells in the spleen and peripheral blood of the recipient B6 mice, but was never observed in the thymus. Moreover, when irradiated F344 cells were used in place of viable cells, chimerism was never detected and graft survival was only slightly prolonged. Clonal deletion of Vβ5- or Vβ11-bearing murine T cells was not observed on day 50 in the thymus or spleen of the recipient B6 mice. These results suggest that treatment with viable xenogeneic donor cells, CP, and mAbs against T and NK cells can induce a temporary peripheral mixed chimerism and donor-specific prolongation of xenogeneic skin graft survival. The destruction with CP of T and B cells that are xenoreactive and thus proliferating after antigen stimulation, followed by mechanisms other than intrathymic clonal deletion, may be the mechanism of the hyporesponsiveness in the present system.
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