The effect of limited courses of cyclosporine on survival and immunocompetence of allogeneic bone marrow chimeras.

Abstract:

:Isolator-maintained CBH/Ola (Rtlc) rats were lethally irradiated and reconstituted with spleen and bone marrow cells from fully allogeneic WAG or Wistar (Rtlu) donors. Hematopoietically reconstituted rats were treated with cyclosporine (CsA)4 as prophylaxis for graft-versus-host disease (GVHD) for periods ranging from 6 to 26 weeks. Following the termination of CsA treatment GVH reactivity developed in all recipients of allogeneic cells regardless of the duration of immunosuppression. Approximately a third of the reconstituted rats survived the post-CsA period of GVH activity; these rats carried peripheral lymphocytes and spleen cells of donor strain origin and were specifically unresponsive to donor strain skin grafts. Surviving chimeras remained healthy for long periods (up to 18 months) after transplantation, although morbidity increased slightly for rats moved to normal animal house conditions. However, all chimeras had some degree of lymphopenia and showed diminished immunological responses to extraneous antigens and third-party skin grafts. Experiments to elucidate the mechanisms by which specific tolerance was maintained in chimeras indicated that neither the deletion of host-reactive lymphocytes from the graft nor an absence of host bone-marrow-derived "stimulator" cells was responsible. It was shown that the potential GVH reactivity of normal donor strain cells was specifically suppressed in vivo (in the chimera) and that this suppression could be transferred to secondary irradiated recipients by transferring chimeric spleen cells. Attempts to demonstrate a role for suppressor cells in the maintenance of the chimeric state yielded inconclusive results.

journal_name

Transplantation

journal_title

Transplantation

authors

Denham S,Attridge SR,Barfoot RK

doi

10.1097/00007890-198511000-00002

subject

Has Abstract

pub_date

1985-11-01 00:00:00

pages

477-82

issue

5

eissn

0041-1337

issn

1534-6080

journal_volume

40

pub_type

杂志文章
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    journal_title:Transplantation

    pub_type: 杂志文章

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    authors: Eberspächer ML,Otto G,Herfarth C,Kabelitz D

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  • Cyclosporine formulation and Kaposi's sarcoma after renal transplantation.

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  • Influence of the hepatic drug-metabolizing enzyme-inducer phenobarbitone on cyclosporine nephrotoxicity and hepatotoxicity in renal-allografted rats.

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