Oral delivery of xeno-antigen combined with non-depleting anti-CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft.
Oral administration can induce unresponsiveness to protein antigens. Therefore, we examined whether oral administration of xeno-antigen could induce the prolonged survival of xenogeneic skin grafts. CBA mice were given 1 x 10(7) SD rat splenocytes orally, 7 days before transplantation of a SD rat skin in the presence or absence of a non-depleting anti-CD4 monoclonal antibody (mAb) (YTS177, 200 microg/dose, 8 and 7 days relative to transplantation). All skin grafts survived with a median survival time (MST) of 62 days when xeno-antigens were administered orally in combination with anti-CD4 mAb. Mice treated with anti-CD4 mAb alone or oral administration of xeno-antigen alone induced modest prolonged survival of rat skin grafts (MST = 18 and 19 days, respectively) while naive mice rejected rat skin acutely (MST= 12 days). Oral administration alone or combined with anti-CD4 mAb reduced the level of xeno-antibody production compared with that in untreated mice after transplantation. Xenogeneic mixed leukocyte response was reduced when splenocytes from mice pre-treated with oral administration of xenogeneic cells were used as the responder compared with that in untreated mice. Oral delivery of xeno-antigen plus non-depleting anti-CD4 mAb can induce prolongation of concordant xenogeneic skin grafts.
Niimi
M
M
First Department of Surgery, Teikyo University, Tokyo, Japan. mniimi@med.teikyo-u.ac.jp
Shirasugi
N
N
Hamano
K
K
Esato
K
K
Matsumoto
K
K
Ikeda
Y
Y
Shatari
T
T
Takami
H
H
Kodaira
S
S
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D015478:Antigens, Heterophile / Q000008:administration & dosage / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D051379:Mice; D051381:Rats; D016038:Skin Transplantation; D014181:Transplantation Immunology; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D015478:Antigens, Heterophile; D015704:CD4 Antigens