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 Zhou, J. Articles by G. Lee, T. D. Search for Related Content PubMed PubMed Citation Articles by Zhou, J. Articles by G. Lee, T. D. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Kidney Transplantation

Oral Exposure to Alloantigen Generates Intragraft CD8⁺ Regulatory Cells¹

Juan Zhou^*,, Ronald I. Carr^*,, Robert S. Liwski^*,, Andrew W. Stadnyk^*, and Timothy D. G. Lee^2,*,

Departments of ^* Microbiology and Immunology, Surgery, Medicine, and Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada

We have previously reported that oral administration of allogeneic rat spleen cells before kidney allotransplantation significantly prolongs graft survival. This prolongation was alloantigen specific and was associated with a decrease in graft-infiltrating cells (GIC) and an increase in transcription of IL-4 mRNA in the GIC. In this study increased splenic mixed lymphocyte responses from animals orally exposed to alloantigen before kidney transplantation suggested that the kidney allograft prolongation was not due to a masking of allorecognition, but to an immunomodulation of the immune response. We have assessed GIC T cell subsets on day 5 post-transplant and found decreased numbers of CD4⁺ T cells in fed animals compared with controls, but there was no change in CD8⁺ T cell numbers. The CD8⁺ GIC from fed animals transcribed substantial levels of perforin, granzyme, and Fas ligand mRNA, indicating the presence of active CTL. Direct CTL assays showed that the GIC from fed recipients exhibited higher allo-CTL activity than GIC from control unfed recipients. In addition, the CD8⁺ GIC exhibited high levels of IL-4 mRNA, suggesting Tc2-type regulatory cells. Prolonged graft survival in the face of active CTL and Tc2 cells suggests the presence of a CD8⁺ regulatory cell population in the allograft. To confirm this, cell transfer experiments were performed. Prolongation of graft survival was transferred from rats orally exposed to alloantigen to naive animals by transfer of CD8⁺ GIC. This is the first report that oral exposure to alloantigen prolongs kidney allograft survival by the generation of intragraft CD8⁺ regulatory cells.

This article has been cited by other articles:

				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]

				W. Chen, D. Zhou, J. R. Torrealba, T. K. Waddell, D. Grant, and L. Zhang Donor Lymphocyte Infusion Induces Long-Term Donor-Specific Cardiac Xenograft Survival through Activation of Recipient Double-Negative Regulatory T Cells J. Immunol., September 1, 2005; 175(5): 3409 - 3416. [Abstract] [Full Text] [PDF]

				Z. Dai, I. W. Nasr, M. Reel, S. Deng, L. Diggs, C. P. Larsen, D. M. Rothstein, and F. G. Lakkis Impaired Recall of CD8 Memory T Cells in Immunologically Privileged Tissue J. Immunol., February 1, 2005; 174(3): 1165 - 1170. [Abstract] [Full Text] [PDF]

				A. I. Skaro, R. S. Liwski, J. Zhou, E. L. Vessie, T. D.G. Lee, and G. M. Hirsch CD8+ T cells mediate aortic allograft vasculopathy by direct killing and an interferon-{gamma}-dependent indirect pathway Cardiovasc Res, January 1, 2005; 65(1): 283 - 291. [Abstract] [Full Text] [PDF]

				S. Vigouroux, E. Yvon, E. Biagi, and M. K. Brenner Antigen-induced regulatory T cells Blood, July 1, 2004; 104(1): 26 - 33. [Abstract] [Full Text] [PDF]

				E. S. Morris, K. P. A. MacDonald, V. Rowe, D. H. Johnson, T. Banovic, A. D. Clouston, and G. R. Hill Donor treatment with pegylated G-CSF augments the generation of IL-10-producing regulatory T cells and promotes transplantation tolerance Blood, May 1, 2004; 103(9): 3573 - 3581. [Abstract] [Full Text] [PDF]

				J. C. Zimring, S. B. Levery, B. Kniep, L. M. Kapp, M. Fuller, and J. A. Kapp CD75s is a marker of murine CD8+ suppressor T cells Int. Immunol., November 1, 2003; 15(11): 1389 - 1399. [Abstract] [Full Text] [PDF]

				M. Kataoka, J. A. Margenthaler, G. Ku, and M. W. Flye Development of Infectious Tolerance After Donor-Specific Transfusion and Rat Heart Transplantation J. Immunol., July 1, 2003; 171(1): 204 - 211. [Abstract] [Full Text] [PDF]

				W. Chen, M. S. Ford, K. J. Young, M. I. Cybulsky, and L. Zhang Role of Double-Negative Regulatory T Cells in Long-Term Cardiac Xenograft Survival J. Immunol., February 15, 2003; 170(4): 1846 - 1853. [Abstract] [Full Text] [PDF]

				K. J. Young, L. Yang, M. J. Phillips, and L. Zhang Donor-lymphocyte infusion induces transplantation tolerance by activating systemic and graft-infiltrating double-negative regulatory T cells Blood, October 16, 2002; 100(9): 3408 - 3414. [Abstract] [Full Text] [PDF]

				E. Chiffoleau, G. Beriou, P. Dutartre, C. Usal, J.-P. Soulillou, and M. C. Cuturi Role for Thymic and Splenic Regulatory CD4+ T Cells Induced by Donor Dendritic Cells in Allograft Tolerance by LF15-0195 Treatment J. Immunol., May 15, 2002; 168(10): 5058 - 5069. [Abstract] [Full Text] [PDF]