Induction of specific unresponsiveness to cardiac allografts by short-term administration of anti-T cell receptor alpha beta antibody.
Organ graft rejection is a T cell-dependent process in which activation of alloreactive T cells via the T cell receptor/CD3 complex is a critical step. Although treatment with anti-CD3 has been shown to prevent and reverse allograft rejection, there is little information available regarding the effects of immunotherapy using anti-TCR alpha beta mAb for rejection. In the present study, short-term preoperative treatment of rats with a mAb against alpha beta TCR (R73) completely prevented the rejection of cardiac allografts. These rats accepted second cardiac allografts from the same donor strain, but not from a third-party strain, without additional treatment. In mixed lymphocyte cultures, T cells from rats that had received cardiac grafts did not respond to donor-strain heart cells, but did respond to donor-strain spleen cells and third-party heart cells. These findings suggest that specific unresponsiveness to cardiac tissue was induced in R73-treated rats. Such unresponsiveness was induced only when rats were pretreated with the mAb and subsequently received a transplant. It is likely that administration of a small dose of R73 induced transient immunomodulation of TCR molecules, resulting in unresponsiveness to a subsequent cardiac allograft. Immunotherapy with mAb against TCR alpha beta is very effective, without apparent side effects, and may provide a new method for preventing graft rejection.
Tsuchida
M
M
Department of Immunology, Niigata University School of Medicine, Japan.
Hirahara
H
H
Matsumoto
Y
Y
Abo
T
T
Eguchi
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D006084:Graft Rejection / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D007167:Immunotherapy; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2