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 Lin, Y. Articles by Waer, M. Search for Related Content PubMed PubMed Citation Articles by Lin, Y. Articles by Waer, M.

Accommodation and T-Independent B Cell Tolerance in Rats With Long Term Surviving Hamster Heart Xenografts¹

Yuan Lin^*, Michel Vandeputte and Mark Waer^2,*

^* Laboratory for Experimental Transplantation and Rega Institute, University of Leuven, Leuven, Belgium

It was previously reported that treatment with leflunomide (LF; 10 mg/kg/day) together with cyclosporine (CsA; 10 mg/kg/day) resulted in long term survival of hamster heart xenografts (Xg) in rats and that LF could be withdrawn 2 to 4 wk after transplantation. To study the mechanisms allowing withdrawal of LF, second hamster heart Xgs were transplanted 6 wk after the first xenograft. Only the rats that received LF for 4 wk accepted second Xgs (>30 days; n = 5). Hence, after 4 wk of LF, the rats developed partial B cell tolerance, as they were unable to produce T-independent (CsA-resistant) XAbs. Rejection of second Xgs (2–4 days; n = 5) in the 2-wk LF group resulted in the formation of IgM xenoantibodies (XAbs) localizing together with complement within rejected grafts. However, these XAbs did not affect first Xgs, suggesting that the latter Xgs became resistant to this IgM XAb-mediated rejection, a phenomenon referred to as accommodation. Accommodation was further confirmed as adoptive transfer of IgM XAbs, which resulted in hyperacute Xg rejection in naive rats (<1 h; n = 5), did not cause rejection in long term survivors (>30 days; n = 4). This was associated with a down-regulation of the expression on the graft endothelial cells of adhesion molecules (believed to be important expressers of xenogeneic epitopes), such as P- and E-selectins. Interestingly, these adhesion molecules reappeared after retransplanting the accommodated Xgs to naive recipients. In conclusion, depending on the duration of the LF treatment, long term survival of hamster hearts in CsA-treated rats is based in part on accommodation and in part on T-independent B cell tolerance.

This article has been cited by other articles:

				M. Cascalho, B. M. Ogle, and J. L. Platt Xenotransplantation and the Future of Renal Replacement J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1106 - 1112. [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]

				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]

				Y. Lin, M. P. Soares, K. Sato, K. Takigami, E. Csizmadia, J. Anrather, and F. H. Bach Rejection of Cardiac Xenografts by CD4+ or CD8+ T Cells J. Immunol., January 15, 1999; 162(2): 1206 - 1214. [Abstract] [Full Text] [PDF]

				D. Yin, L. L. Ma, L. Blinder, J. Shen, H. Sankary, J. W. Williams, and A. S.-F. Chong Induction of Species-Specific Host Accommodation in the Hamster-to-Rat Xenotransplantation Model J. Immunol., August 15, 1998; 161(4): 2044 - 2051. [Abstract] [Full Text] [PDF]