Prolongation of renal allograft survival in the rat by pretreatment with donor antigen and cyclosporin A.

Abstract:

:Pretreatment of LEW rats with cyclosporin A (10 mg/kg/day orally for 14 days) plus 10(8) DA or (DA X LEW)F1 spleen lymphocytes on two occasions markedly prolonged the survival of subsequent DA renal allografts. The lymphocytotoxic antibody response was suppressed completely and renal biopsies showed a marked mononuclear cell infiltrate, but no other manifestations of rejection. Neither pretreatment with cyclosporin A alone nor pretreatment with splenic lymphocytes alone had any effect on the subsequent immune reaction. The immunosuppressive effect generated was dependent upon the dose of lymphocytes given, because pretreatment with 10(7) cells on two occasions plus cyclosporin A was relatively ineffective at prolonging renal allograft survival. Pretreatment with 10(8) (DA X LEW)F1 spleen cells plus cyclosporin A was also an effective combination, and ruled out the possibility that graft-versus-host (GVH) disease was responsible for the observed immunosuppression. This pretreatment protocol exhibited specificity in terms of rejection of a third-party (PVG) renal allograft, but not in terms of the lymphocytotoxic antibody response to this graft. Chimerism was not detected in long-term surviving animals using a 51Cr release assay. When pretreatment was performed in LEW rats with a DA skin allograft plus cyclosporin A, a subsequent DA renal allograft was rejected normally, in combination with the skin graft. These findings suggest that clonal deletion had not occurred in these pretreatment protocols, but that a shift in immunoregulatory mechanisms was responsible for the long survival. There are possible clinical implications for the use of pretreatment schedules using donor antigen and cyclosporin A.

journal_name

Transplantation

journal_title

Transplantation

authors

Homan WP,Williams KA,Millard PR,Morris PJ

doi

10.1097/00007890-198106000-00004

subject

Has Abstract

pub_date

1981-06-01 00:00:00

pages

423-7

issue

6

eissn

0041-1337

issn

1534-6080

journal_volume

31

pub_type

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