Importance of thymus to maintain operational tolerance to fully allogeneic cardiac grafts.
BACKGROUND
The effectiveness of donor-specific blood transfusion (DST) before transplantation has been established. Anti-CD4 monoclonal antibody (anti-CD4) augments the ability of DST to induce indefinite prolongation. Therefore, we investigated the importance of thymus to maintain the unresponsiveness to alloantigens.


METHODS
CBA mice were pretreated with 0.25 mL of DST or two doses of anti-CD4 before transplantation of a C57BL/10 heart. Some mice were thymectomized.


RESULTS
Naive CBA mice rejected C57BL/10 grafts acutely with a median survival time of 7 days. When mice were pretreated with anti-CD4 plus DST 4 weeks before transplantation, all grafts survived indefinitely (>100 days), whereas mice treated with DST alone or anti-CD4 alone rejected acutely (median survival time, 7 and 12 days, respectively). To investigate the importance of thymus, mice pretreated with anti-CD4 plus DST 4 weeks before transplantation were thymectomized or underwent a sham operation 1 day before grafting. Mice with the sham operation accepted grafts indefinitely, whereas thymectomized mice rejected the majority of the grafts (median survival time, 20 days).


CONCLUSIONS
The thymus is important in maintaining the operational tolerance induced by anti-CD4 plus DST 4 weeks before grafting.
Niimi
M
M
First Department of Surgery, Teikyo University, Tokyo, Japan. mniimi@med.teikyo-u.ac.jp
Shirasugi
N
N
Ikeda
Y
Y
Kan
S
S
Takami
H
H
Hamano
K
K
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001789:Blood Group Antigens / Q000276:immunology; D001803:Blood Transfusion; D015704:CD4 Antigens / Q000276:immunology; D005434:Flow Cytometry; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007519:Isoantigens / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*; D023001:Transplantation Tolerance
D000911:Antibodies, Monoclonal; D001789:Blood Group Antigens; D015704:CD4 Antigens; D007519:Isoantigens