HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yin, D. Articles by Chong, A. S.-F. Search for Related Content PubMed PubMed Citation Articles by Yin, D. Articles by Chong, A. S.-F.

Induction of Species-Specific Host Accommodation in the Hamster-to-Rat Xenotransplantation Model¹

Section of Transplantation, Department of General Surgery, Rush Presbyterian St. Luke’s Medical Center, Chicago, IL 60612

The combination of two immunosuppressants, leflunomide and cyclosporin A (CsA), completely inhibits immune xenoreactions in the hamster-to-Lewis rat xenotransplantation model. In addition, the control of acute xenograft rejection with this combination of immunosuppressants subdues early T-independent xenoreactivity and uncovers a late immune response that can be controlled by CsA alone. We attribute this acquired responsiveness to CsA to a modification in the recipient’s humoral response to the xenograft, and refer to this change as host accommodation. Host accommodation can be induced in Lewis rats receiving hamster hearts by the combination of leflunomide and CsA. A 7-day treatment with leflunomide and CsA was able to convert xenoreactivity from one that was resistant to CsA treatment into one that was controlled by CsA. The presence of the hamster xenograft was critical for the induction of host accommodation since the immunosuppressive regimen, either alone or in combination with a transfusion with donor-specific spleen cells, was unable to modify the anti-hamster reactivity in Lewis rats. When accommodation was induced in the presence of hamster hearts, these accommodated rats were able to acutely reject third-party mouse hearts while under CsA therapy, thus indicating that the host accommodation is species specific. Finally, we demonstrate that host accommodation is associated with a loss in the ability to produce species-specific, T-independent xenoantibodies. These novel observations suggest that xenoreactive T-independent humoral responses can be deleted selectively without significant loss of other innate, Ag-specific T-independent humoral responses.

This article has been cited by other articles:

				Y. Li, L. Ma, D. Yin, J. Shen, and A. S. Chong Long-Term Control of Alloreactive B Cell Responses by the Suppression of T Cell Help J. Immunol., May 1, 2008; 180(9): 6077 - 6084. [Abstract] [Full Text] [PDF]

				C. A. Koch, Z. I. Khalpey, and J. L. Platt Accommodation: Preventing Injury in Transplantation and Disease J. Immunol., May 1, 2004; 172(9): 5143 - 5148. [Abstract] [Full Text] [PDF]

				D. Yin, L. Ma, A. Varghese, J. Shen, and A. S.-F. Chong Intact Active Bone Transplantation Synergizes with Anti-CD40 Ligand Therapy to Induce B Cell Tolerance J. Immunol., May 15, 2002; 168(10): 5352 - 5358. [Abstract] [Full Text] [PDF]

				Y. Lin, M. P. Soares, K. Sato, E. Csizmadia, S. C. Robson, N. Smith, and F. H. Bach Long-Term Survival of Hamster Hearts in Presensitized Rats J. Immunol., May 1, 2000; 164(9): 4883 - 4892. [Abstract] [Full Text] [PDF]

				Y. Lin, M. P. Soares, K. Sato, K. Takigami, E. Csizmadia, N. Smith, and F. H. Bach Accommodated Xenografts Survive in the Presence of Anti-Donor Antibodies and Complement That Precipitate Rejection of Naive Xenografts J. Immunol., September 1, 1999; 163(5): 2850 - 2857. [Abstract] [Full Text] [PDF]