Induction of Transplantation Tolerance by Feeding or Portal Vein Injection Pretreatment of Recipient with Donor Cells

Carr, Ronald I.; Ledingham, D L; Maloney, Catherine; McAlister, Vivian C.; Samson, Michel; Bitter-Suermann, H; Lee, Timothy D.G.

doi:10.1111/j.1749-6632.1996.tb21145.x

Cited by 8 publications

(9 citation statements)

References 9 publications

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“…Weiner and colleagues reported that oral administration of allogeneic splenocytes ameliorated allosensitization by skin grafting, but only observed effects on second set (not primary) rejection of solid organ allografts with their feeding protocol (5,6). We subsequently demonstrated, using a different protocol, that feeding allosplenocytes significantly prolonged kidney allograft survival in rats (7,8). This prolongation was alloantigen specific (8).…”

mentioning

confidence: 68%

“…In the experiments described here we have examined whether the generation of such regulatory cells plays a role in the significant prolongation of primary kidney allograft survival that we have observed following oral exposure to alloantigen (7,8). We first assessed allorecognition by MLR in fed vs control animals.…”

Section: Discussionmentioning

confidence: 99%

“…ϩ GIC It has been suggested that oral tolerance can generate CD8 ϩ regulatory cells (14,20) and/or switch immune responses toward type 2 responses (7,12,17). Because in our experiments the number of CD8 ϩ GIC T cells remains the same in fed and unfed animals, but grafts survived much longer in the fed animals, we postulated that the phenotype of the CD8 ϩ GIC T cells may have shifted to a type 2 CD8 ϩ T cell phenotype (Tc2).…”

Section: Cytokine Transcription Of Cd8mentioning

confidence: 99%

“…Although oral tolerance has been extensively studied in autoimmune disease models, it is only recently that oral tolerance has been demonstrated to prolong first-set transplant survival (7)(8)(9). As such, the mechanisms responsible for this graft prolongation by oral administration of alloantigen are still unclear.…”

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confidence: 99%

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Oral Exposure to Alloantigen Generates Intragraft CD8+ Regulatory Cells

Zhou

Carr

Liwski

et al. 2001

The Journal of Immunology

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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.

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mentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Cytokine Transcription Of Cd8mentioning

confidence: 99%

mentioning

confidence: 99%

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Oral Exposure to Alloantigen Generates Intragraft CD8+ Regulatory Cells

Zhou

Carr

Liwski

et al. 2001

The Journal of Immunology

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“…The antigen may stimulate cells from the gastrointestinal lymphoid tissue system to produce regulatory cytokines, such as transforming growth factor-ß (TGF-ß), interleukin-10 (IL-10) and IL-4 (3). Induction of tolerance has also been observed when donor cells are injected into the portal vein, with prolongation of renal allograft survival (11). The effect of portal vein antigen injection on allogeneic graft acceptance in mice may involve γ/δTCR+ producers of Th2 cytokines (12).…”

Section: Introductionmentioning

confidence: 99%

Induction of oral tolerance and the effect of interleukin-4 on murine skin allograft rejection

Dettino

Duarte

Sato

2004

Braz J Med Biol Res

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Effects of Schwann cells and donor antigen on long-nerve allograft regeneration

et al. 2005

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Nerve allotransplantation has been used successfully in human subjects to restore function after traumatic nerve injury and avoid subsequent limb amputation. However, due to the morbidity associated with nonspecific immunosuppression, this reconstructive approach has been limited to patients with particularly severe nerve injuries. It would be desirable to broaden the indications for such procedures through development of less toxic antirejection therapies. A miniature swine model of nerve transplantation was used to investigate the effects of preoperative ultraviolet-B (UV-B)-irradiated donor alloantigen portal venous infusion and injection of cultured major histocompatibility complex (MHC)-matched Schwann cells into the nerve graft. The transplanted ulnar nerves were harvested at 20 weeks. Histomorphometry showed marked enhancement in nerve regeneration through allografts injected with Schwann cells. Serial mixed lymphocyte assays demonstrated suppression of the recipient immune response to the donor antigen after pretreatment, but no additional neuroregenerative effect of donor alloantigen pretreatment.

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Induction of Transplantation Tolerance by Feeding or Portal Vein Injection Pretreatment of Recipient with Donor Cells

Cited by 8 publications

References 9 publications

Oral Exposure to Alloantigen Generates Intragraft CD8+ Regulatory Cells

Oral Exposure to Alloantigen Generates Intragraft CD8+ Regulatory Cells

Induction of oral tolerance and the effect of interleukin-4 on murine skin allograft rejection

Effects of Schwann cells and donor antigen on long-nerve allograft regeneration

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