Histone H1 Vaccine Therapy for Overcoming Acute Rejection in Experimental Organ Transplantation

• Published in: Transplantation proceedings 2006-12, Vol.38 (10), p.3247-3248
• Main Authors: Nakano, T., Ono, K., Goto, S., Lai, C.-Y., Hsu, L.-W., Kawamoto, S., Lin, Y.-C., Kao, Y.-H., Chiang, K.-C., Ohmori, N., Goto, T., Sato, S., Jawan, B., Cheng, Y.-F., Chen, C.-L.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Graft Rejection - immunology; Graft Rejection - prevention & control; Graft Survival - immunology; Heart Transplantation - immunology; Histones - immunology; Liver Transplantation - immunology; Lymphocyte Culture Test, Mixed; Medical sciences; Prevention and actions; Public health. Hygiene; Public health. Hygiene-occupational medicine; Rats; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T-Lymphocytes - immunology; Tissue, organ and graft immunology; Vaccination
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2006.10.078

In a rat tolerogenic orthotopic liver transplantation (OLT) model, the recipient serum (post-OLT serum) shows strong immunosuppressive activity. In our previous reports, we suggested that autoreactive antibody (Ab) against histone H1 is a major immunosuppressive factor in this serum. The present study sought to determine whether up-regulation of anti-histone H1 Ab by histone H1 vaccination led to tolerance. Using mixed lymphocyte reactions (MLR) and heterotopic heart transplantations (HHT), the alloreactive T-cell responses and allograft survivals of histone H1-immunized rats were compared with those of control rats. Cytokine and cellular profiles were determined by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. The alloreactive T-cell response of histone H1-immunized rats was significantly lower than that of control rats, although there was no difference in nonspecific T-cell activation between the 2 groups. The allograft survival of histone H1-immunized rats was significantly prolonged after HHT. The major histocompatibility complex (MHC) class II and CD25 molecules of histone H1-immunized rats were significantly down-regulated compared with those of control rats. Moreover, the serum cytokine profile was modified by the immunization with histone H1. These results suggest that histone H1 vaccination of transplant recipients leads to the production of immunosuppressive factors and the modification of cytokine/cellular profiles.