| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Thorac Cardiovasc Surg 2001;122:629-630
© 2001 The American Association for Thoracic Surgery
Brief Communications |
From the First Department of Surgery, Teikyo University School of Medicine, Tokyo,a and the First Department of Surgery, Yamaguchi University School of Medicine, Yamaguchi, Japan.b
Received for publication Jan 18, 2001. Accepted for publication Feb 6, 2001. Address for reprints: Masanori Niimi, MD, DPhil, First Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, Japan 173-8605 (E-mail: mniimi{at}med.teikyo-u.ac.jp).
Oral administration can induce unresponsiveness to protein antigens.
1 We have already shown that oral delivery of donor splenocytes induces prolonged survival of allogeneic or xenogeneic grafts when delivered with a nondepleting anti-CD4 monoclonal antibody (anti-CD4). 2,3 Intravenous injection of a single major histocompatibility complex (MHC) molecule has been shown to induce prolongation of fully MHC-mismatched grafts. 4 This phenomenon can be explained by the linked suppression, 4,5 in which tolerance to strain (AxB)F1 is also established when recipients become tolerant to strain A. Therefore, we have examined whether a single donor MHC antigen or soluble ovalbumin (OVA) could induce survival of fully MHC-mismatched cardiac grafts when delivered into the alimentary tract with anti-CD4.
Mice (8-12 weeks of age) were purchased from Sankyo (Tokyo, Japan) and housed in conventional facilities of the Biomedical Services Unit, Teikyo Hospital, Tokyo, and used in accordance with the Animal Care Guidelines of Teikyo University. Mouse hearts were transplanted into the abdomen of a recipient by means of a microsurgical technique. 2 Naive CBA (H2k) mice fully rejected allogeneic C57BL/10 (H2b) cardiac grafts, with 8 days of median survival time (MST; Table 1). When CBA mice were fed with 1 x 107 C57BL/10 splenocytes (day –7) combined with intraperitoneal injection of a nondepleting anti-CD4 (days –8 and –7, 200 µg per dose, YTS 1772; hybridoma kindly provided by H. Waldmann, Oxford, United Kingdom), the majority of grafts survived indefinitely (MST >100 days,Table 1), whereas mice pretreated orally with splenocytes alone or with anti-CD4 alone rejected their grafts (MST = 8 and 7.5 days inTable 1). Intravenous injection of C57BL/10 splenocytes combined with the anti-CD4 was less effective (MST = 15 days, data not shown), suggesting that alloantigen delivery though the alimentary tract is essential to induce graft survival. Furthermore, when splenocytes from CBK mice (an MHC class I, Kb, transgenic strain [H2k+Kb] in the context of CBA 4) were used for oral pretreatment in combination with anti-CD4, all C57BL/10 grafts survived for more than 100 days(Table 1). Therefore, oral exposure to a single donor alloantigen Kb was sufficient to induce unresponsiveness to a fully allogeneic C57BL/10 (H2b: Kb+Db+Lb+IAb) cardiac graft, which can be explained by the linked suppression. 4,5 On the other hand, we have already shown that orally delivered cells are degraded and that alloantigens may be presented on MHC molecules of the recipient (ie, indirect allorecognition). 2 The direct antigen recognition, in which recipient T cells directly recognize MHC molecules on donor cells, mainly generates acute rejection of a fully MHCmismatched graft. Taken together, these findings suggest that the linked suppression through the indirect pathway is involved in survival of cardiac allografts in this model. Therefore, we speculated that not only an MHC molecule but also a foreign protein antigen can induce graft prolongation when delivered orally with anti-CD4 and presented at the time of transplantation. In an attempt to confirm this hypothesis, we fed CBA mice with 50 mg of OVA (day –7) in the presence of anti-CD4 (days –8 and –7). All C57BL/10 grafts survived for more than 50 days when 50 mg of OVA was again fed at the time of transplantation (MST >100 days,Table 1). By contrast, mice only receiving OVA at the time of pretreatment rejected their grafts within 50 days (MST = 24 days,Table 1), demonstrating that a foreign peptide can induce unresponsiveness to MHC molecules when pretreated orally with anti-CD4 and presented at the same time of transplantation.
|
1 Recipients pretreated with oral administration of a common MHC antigen in the presence of anti-CD4 may be tolerant to an allogeneic organ sharing the MHC antigen, even if the other MHC antigens are mismatched. 2 A recipient pretreated with oral administration of a foreign antigen in combination with anti-CD4 may accept any allogeneic organs when the foreign antigen coexists at the time of transplantation. References
This article has been cited by other articles:
|
|
 |
|
  O. Aramaki, N. Shirasugi, Y. Akiyama, Y. Ikeda, S. Yabuki, M. Shimazu, M. Kitajima, and M. Niimi Prolonged survival of fully allogeneic cardiac grafts in naive mice and those with sensitization induced by antigen delivery through the respiratory tract J. Thorac. Cardiovasc. Surg., September 1, 2003; 126(3): 853 - 854. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
