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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nasr, I. W. Articles by Dai, Z. Search for Related Content PubMed PubMed Citation Articles by Nasr, I. W. Articles by Dai, Z. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Islet Cell Transplantation

Testicular Immune Privilege Promotes Transplantation Tolerance by Altering the Balance between Memory and Regulatory T Cells ¹

Isam W. Nasr^*, Yinong Wang, Ge Gao, Songyan Deng^*, Lonnette Diggs^*, David M. Rothstein^*, George Tellides, Fadi G. Lakkis^* and Zhenhua Dai^2,

^* Section of Nephrology, Department of Internal Medicine and Section of Immunobiology, Section of Cardiothoracic Surgery, Department of Surgery, Section of Cardiology, Yale University School of Medicine, New Haven, CT 06520; and Center for Biomedical Research, University of Texas Health Center at Tyler, Tyler, TX 75708

Immune responses are suppressed in immunologically privileged sites, which may provide a unique opportunity to prolong allograft survival. However, it is unknown whether testicular immune privilege promotes transplantation tolerance. Mechanisms underlying immune privilege are also not well understood. Here we found that islet transplantation in the testis, an immunologically privileged site, generates much less memory CD8⁺ T cells but induces more Ag-specific CD4⁺CD25⁺ regulatory T cells than in a conventional site. These CD4⁺CD25⁺ cells exhibited the suppression of alloimmune responses in vivo and in vitro. Despite the immune regulation, intratesticular islet allografts all were rejected within 42 days after transplantation although they survived longer than renal subcapsular islet allografts. However, blocking CD40/CD40L costimulation induced the tolerance of intratesticular, but not renal subcapsular, islet allografts. Tolerance to intratesticular islet allografts spread to skin allografts in the non-privileged sites. Either transfer of memory CD8⁺ T cells or deletion of CD25⁺ T cells in vivo broke islet allograft tolerance. Thus, transplantation tolerance requires both costimulatory blockade, which suppresses acute allograft rejection, and a favorable balance between memory and regulatory T cells that could favorably prevent late allograft failure. These findings reveal novel mechanisms of immune privilege and provide direct evidence that testicular immune privilege fosters the induction of transplantation tolerance to allografts in both immunologically privileged and non-privileged sites.

This article has been cited by other articles:

				L. M. Foulds, R. I. Boysen, M. Crane, Y. Yang, J. A. Muir, A. I. Smith, D. M. d. Kretser, M. T.W. Hearn, and M. P. Hedger Molecular Identification of Lyso-Glycerophosphocholines as Endogenous Immunosuppressives in Bovine and Rat Gonadal Fluids Biol Reprod, September 1, 2008; 79(3): 525 - 536. [Abstract] [Full Text] [PDF]

				K.-H. Grinnemo, R. Genead, M. Kumagai-Braesch, A. Andersson, C. Danielsson, A. Mansson-Broberg, G. Dellgren, A.-M. Stromberg, H. Ekberg, O. Hovatta, et al. Costimulation Blockade Induces Tolerance to HESC Transplanted to the Testis and Induces Regulatory T-Cells to HESC Transplanted into the Heart Stem Cells, July 1, 2008; 26(7): 1850 - 1857. [Abstract] [Full Text] [PDF]

				T. Wang, H. Dai, N. Wan, Y. Moore, and Z. Dai The Role for Monocyte Chemoattractant Protein-1 in the Generation and Function of Memory CD8+ T Cells J. Immunol., March 1, 2008; 180(5): 2886 - 2893. [Abstract] [Full Text] [PDF]

				V. Dal Secco, A. Riccioli, F. Padula, E. Ziparo, and A. Filippini Mouse Sertoli Cells Display Phenotypical and Functional Traits of Antigen-Presenting Cells in Response to Interferon Gamma Biol Reprod, February 1, 2008; 78(2): 234 - 242. [Abstract] [Full Text] [PDF]

				N. Wan, H. Dai, T. Wang, Y. Moore, X. X. Zheng, and Z. Dai Bystander Central Memory but Not Effector Memory CD8+ T Cells Suppress Allograft Rejection J. Immunol., January 1, 2008; 180(1): 113 - 121. [Abstract] [Full Text] [PDF]

				Z. Liu, H. Dai, N. Wan, T. Wang, S. Bertera, M. Trucco, and Z. Dai Suppression of Memory CD8 T Cell Generation and Function by Tryptophan Catabolism J. Immunol., April 1, 2007; 178(7): 4260 - 4266. [Abstract] [Full Text] [PDF]

				J. Stein-Streilein and A. W. Taylor An eye's view of T regulatory cells J. Leukoc. Biol., March 1, 2007; 81(3): 593 - 598. [Abstract] [Full Text] [PDF]

				C. K. Zetterstrom, M.-L. Strand, and O. Soder The high mobility group box chromosomal protein 1 is expressed in the human and rat testis where it may function as an antibacterial factor Hum. Reprod., November 1, 2006; 21(11): 2801 - 2809. [Abstract] [Full Text] [PDF]