Recombinant IFN‐γ abrogates allograft tolerance induced by donor‐specific blood transfusion by restoring alloantibody production

Donor‐specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donor‐specific blood transfusion (DST). We previously showed that this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount a...

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Bibliographic Details
Published in:European journal of immunology 1999-01, Vol.29 (1), p.317-326
Main Authors: Josien, Régis, Cuturi, Maria‐Cristina, Douillard, Patrice, Heslan, Michèle, Heslan, Jean‐Marie, Soulillou, Jean‐Paul
Format: Article
Language:English
Subjects:
AIDS/HIV
Allograft
Animals
Base Sequence
Blood Transfusion
Cytokines - genetics
DNA Primers - genetics
Heart Transplantation - immunology
IFN‐γ
Immune Tolerance - drug effects
Immunoglobulin G - biosynthesis
In Vitro Techniques
Interferon-gamma - pharmacology
Isoantibodies - biosynthesis
Lymphocyte Activation
Macrophage Activation
Male
Rats
Rats, Inbred Lew
Recombinant Proteins
Rejection
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodent
Th1 Cells - immunology
Tissue Donors
Tolerance
Transforming Growth Factor beta - genetics
Transplantation Immunology - drug effects
Transplantation, Homologous
Citations: Items that this one cites
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Summary:Donor‐specific tolerance to heart allograft was induced in adult Lewis rats by pregraft donor‐specific blood transfusion (DST). We previously showed that this tolerant state is characterized by a dramatic inhibition of T cell and macrophage activation. In addition, tolerant animals could not mount an efficient anti‐donor humoral response whereas transfer of sera from rejecting animals triggered rejection in tolerant animals. This tolerance can be abrogated by daily post‐graft administration of recombinant IFN‐γ (rIFN‐γ). To elucidate the mechanisms of action of rIFN‐γ, T cell, macrophage and B cell functions were assessed in allograft recipients. IFN‐γ did not restore the expression of Th1‐related cytokine mRNA or the activated macrophage product inducible nitric oxide synthase in allografts. Importantly, rIFN‐γ treatment promptly restored the anti‐donor humoral response in DST‐treated recipients. We conclude that rIFN‐γ treatment in DST‐treated allograft recipients cannot reverse the unresponsive state of Th1 cells and macrophages infiltrating the graft, but can provide B cell help for IgG alloantibody production which is lacking in these animals.
ISSN:0014-2980
1521-4141
DOI:10.1002/(SICI)1521-4141(199901)29:01<317::AID-IMMU317>3.0.CO;2-O