Tolerance in a rat cardiac allograft model after short-term treatment with LF 08-0299. Absence of clonal deletion and evidence of CD4+ suppressor cells

Transplantation
C AndoinsP Dutartre

Abstract

LF 08-0299 is a new immunosuppressive compound. In a fully mismatched rat cardiac allograft model (Dark Agouti [DA]-->Lewis [LEW]), long-term unresponsiveness was observed after LF 08-0299 short-term treatment (20 days). Survival of additional cardiac and skin DA allografts, and rejection of third-party (Brown Norway [BN]) skin allografts demonstrated induction of a donor-specific tolerance state. The aim of this study was to investigate mechanisms of cardiac acceptance in this model. LEW rats with long-term surviving heart grafts (LTS LEW) were examined for their immune proliferative and cytotoxic responses toward donors (DA) and third-party (BN) antigens. Normal proliferative responses were observed and limiting dilution analysis did not reveal a reduction of T cytotoxic cell precursors. In our model, tolerance exists despite the presence of cells reactive with donor alloantigens. In vivo adoptive transfer of serum from LTS LEW failed to transfer unresponsiveness, indicating that serum factors do not seem to be involved in tolerance maintenance. Transfer of spleen cells, obtained from LTS LEW, showed specific prolongation of DA cardiac allografts in syngeneic hosts. Moreover, these cells were able to induce the rejection of t...Continue Reading

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Citations

Oct 6, 1999·Current Opinion in Immunology·Y Zhai, J W Kupiec-Weglinski
Apr 11, 2003·Fundamental & Clinical Pharmacology·P ClaudR Laine
Jul 14, 2000·Journal of Hematotherapy & Stem Cell Research·D Simpson
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Sep 24, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Elise ChiffoleauMaria Cristina Cuturi
May 23, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Philippe ClaudRomuald Laine
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elise ChiffoleauMaria Cristina Cuturi

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