Transfer of “infectious” cardiac allograft tolerance induced by donor-specific transfusion

• Published in: Surgery 2002-08, Vol.132 (2), p.167-172
• Main Authors: Kataoka, Masaaki, Shimizu, Yoshiaki, Margenthaler, Julie A., Landeros, Keith, Otomo, Naoki, Flye, M.Wayne
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antibodies, Monoclonal - pharmacology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - immunology; Graft Rejection - therapy; Graft Survival - immunology; Heart Transplantation - immunology; Immune Tolerance - immunology; Immunobiology; Immunoglobulins, Intravenous; Male; Medical sciences; Modulation of the immune response (stimulation, suppression); Rats; Rats, Inbred BN; Rats, Inbred Lew; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Transplantation, Homologous
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1067/msy.2002.125303

Background. “Infectious tolerance” has been defined as the tolerance induced in a new recipient by the adoptive transfer of cells from a recipient accepting an allograft after anti-CD4 and anti-CD8 monoclonal antibody treatment. A clear understanding of the mechanisms responsible for graft acceptance after donor-specific blood transfusion (DST) has remained elusive. We examined the development and “infectious” nature of immunologic changes resulting in indefinite survival of LEW to DA rat cardiac allografts after DST alone without the need for antibody. Methods. One hundred × 106 LEW splenocytes (SC) as DST were injected intravenously into DA recipients 7 days before LEW cardiac transplantation. Subsequently, 100 × 106 SC harvested from a DA recipient 30, 60, or 100 days after graft acceptance were adoptively transferred into lightly γ-irradiated (450 rad) naïve DA recipients 24 hours before a second LEW cardiac allograft. Subsequent graft function was determined. Results. Adoptive transfer of SC from the DST-treated DA rats 30 days after LEW heart transplant acceptance into naïve γ-irradiated DA rats failed to transfer tolerance to LEW cardiac allografts. However, SC from DA rats bearing LEW hearts for more than 60 days induced indefinite tolerance to all LEW hearts. This infectious tolerance could be adoptively transferred again to a second DA recipient. Conclusions. DST-generated regulatory cells can downregulate naïve lymphocytes to promote allograft acceptance. This tolerance can be expanded and serially transferred to a subsequent naïve cardiac recipient. (Surgery 2002;132:167-72.)