Oral delivery of xeno‐antigen combined
with non‐depleting anti‐CD4 monoclonal antibody induces significantly prolonged survival of concordant skin xenograft

• Published in: Xenotransplantation (Københaven) Vol. 8; no. 1; pp. 75 - 79
• Main Authors: Niimi, M., Shirasugi, N., Hamano, K., Esato, K., Matsumoto, K., Ikeda, Y., Shatari, T., Takami, H., Kodaira, S.
• Format: Journal Article
• Language: English
• Published: Copenhagen, Denmark Munksgaard International Publishers 01.02.2001
• Subjects: Administration, Oral; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Antigens, Heterophile - administration & dosage; Antigens, Heterophile - immunology; anti‐CD4 monoclonal antibody; CD4 Antigens - immunology; Graft Rejection - prevention & control; Graft Survival; Mice; oral tolerance; Rats; skin grafts; Skin Transplantation; Transplantation Immunology; Transplantation, Heterologous; xenotransplantation
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1034/j.1399-3089.2001.00080.x

: 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 × 107 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 µg/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.