The Mechanism of the Induction of Immunologic Unresponsiveness to Rat Cardiac Allografts by Recipient Pretreatment With Donor Lymphocyte Subsets

Oluwole, Soji F.; Ng, Ah‐Kau; Reemtsma, K; Hardy, Mark A.

doi:10.1097/00007890-198908000-00020

Cited by 18 publications

(10 citation statements)

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“…Regulatory T cells have also been described in the induction of transplantation tolerance (3) and, more frequently, in the maintenance phase of tolerance occurring in the 50-to 100-day period after transplantation (20 -22). These latter suppressive T cells have been reported to belong to both CD4 and CD8 cell subtypes: either CD8 ϩ only (20) or both CD4 ϩ and CD8 ϩ (21) or more often CD4 ϩ solely (3,21,23). Donor-specific suppressive CD4 ϩ T cells have been found in DST-treated rats (3), but our study suggests that CD8…”

Section: Anti-tcr Vb18 Dna Vaccination Restores Anti-donor Igg Alloancontrasting

confidence: 51%

Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+ T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion

Vignes

Chiffoleau

Douillard

et al. 2000

The Journal of Immunology

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Donor-specific allograft tolerance can be induced in the adult rat by pregraft donor-specific blood transfusion (DST). This tolerance appeared to be mediated by regulatory cells and to the production of the suppressive cytokine TGF-β1. A potential immunoregulatory CD8+ clone bearing a Vβ18-Dβ1-Jβ2.7 TCR gene rearrangement was previously identified in DST-treated recipients. To assess the functional role of this T cell clone in the induction of tolerance by DST, we have vaccinated DST-treated recipients with a plasmid construct encoding for the Vβ18-Dβ1-Jβ2.7 TCR β-chain. DST-induced allograft tolerance was abolished by anti-TCR Vβ18-Dβ1-Jβ2.7 DNA vaccination in six of seven recipients, whereas vaccination with the vector alone, or with the construct encoding a TCR Vβ13 β-chain, had no effect. However, the transcript number of the Vβ18-Dβ1-Jβ2.7 chain was unchanged in allografts from vaccinated DST-treated rats, suggesting that this clone was not depleted by vaccination, but rather was altered in its function. Moreover, TCR Vβ18-Dβ1-Jβ2.7 DNA vaccination restored the anti-donor alloantibody production, partially restore the capacity of spleen cells from tolerized recipients to proliferate in vitro against donor cells, and decreased the inhibitory effect of TGF-β1, seen in DST-treated recipients, in spleen cells from vaccinated DST-treated ones. This study strongly suggests that this CD8+ TCR Vβ18-Dβ1-Jβ2.7 T cell clone has an effective immunoregulatory function in allograft tolerance induced by DST.

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Section: Anti-tcr Vb18 Dna Vaccination Restores Anti-donor Igg Alloancontrasting

confidence: 51%

Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+ T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion

Vignes

Chiffoleau

Douillard

et al. 2000

The Journal of Immunology

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“…These results also suggest that defective alloantigen presentation due to blockade of CD40-CD40L interactions and decrease of CD4 + T cells may participate in the generation of CD8 + CD45RC low cells. CD8 + Tregs have been described in several models (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In allotransplantation models, CD8 + CD28 -Tregs were induced by in vitro allogeneic stimulation of human cells (11) or by DST treatment in rats (4).…”

Section: Discussionmentioning

confidence: 99%

“…2). Although several CD4 + populations have been described as being Tregs, CD8 + Tregs have also been identified in different models (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). One example of CD8 + Tregs is the non-cytokinesecreting, CD8 + CD28 -alloantigen-specific Treg, which interacts directly with DCs or ECs and renders them tolerogenic (4,11).…”

Section: Introductionmentioning

confidence: 99%

CD40Ig treatment results in allograft acceptance mediated by CD8+CD45RClow T cells, IFN-γ, and indoleamine 2,3-dioxygenase

Guillonneau

Hill²,

Hubert³

et al. 2007

J. Clin. Invest.

170

235

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“…Padberg et al (14) demonstrated that both CD4 ϩ and CD8 ϩ T cells from LTS, induced by DST plus hyperimmune serum treatment, suppressed rat heart transplant rejection when adoptively transferred to a naive recipient. Oluwole et al (15) showed that adoptive transfer of 5 ϫ 10 6 LEW DST induced LTS ACI CD8 ϩ T cells prolonged subsequent LEW heart graft survival in an unmodified ACI recipient. Douillard et al (18) found that the expansion of a CD8 ϩ clone bearing the V␤18-D␤1-J␤2.7 TCR gene rearrangement specific for donor MHC was detected in each LEW.1A rat that was tolerized to LEW.1W hearts after DST.…”

Section: Discussionmentioning

confidence: 99%

“…Donor-specific transfusions (DST) 3 induce both experimental and clinical donor-specific allograft tolerance (15,18,19,(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Development Of Infectious Tolerance After Donor-specificmentioning

confidence: 99%

Development of Infectious Tolerance After Donor-Specific Transfusion and Rat Heart Transplantation

Kataoka

Margenthaler

et al. 2003

The Journal of Immunology

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Regulatory cells developed after donor-specific transfusion (DST)-induced acceptance of a LEW heart transplanted into a DA rat. Both DST and the cardiac transplant were necessary to generate the regulatory cells. This donor-specific tolerance can then be transferred into a new DA recipient by adoptive transfer of lymphocytes from the DST-treated long term survivor (LTS) in a dose-dependent manner. The effectiveness of tolerance did not diminish over five generations of adoptive transfer, thus supporting its infectious nature. Although both spleen and lymph node cells were equally effective, graft-infiltrating lymphocytes were more potent. A high level of indirect CTL activity and MLC proliferation were observed in lymphocytes from LTS. In vivo tracking of adoptively transferred CFSE-labeled splenocytes from LTS showed equivalent FACS proliferation and a higher percentage of graft-infiltrating lymphocytes 7 days after heart transplantation, compared with adoptively transferred naive splenocytes. Adoptive transfer of CD8+-depleted LTS splenocytes resulted in 100% subsequent LEW allograft acceptance; whereas CD4+ depletion decreased acceptance to 40%, and depletion of both CD4 and CD8 resulted in 0% acceptance. When positively selected CD4+ or CD8+ cells were adoptively transferred, 100% or 62.5% of LEW cardiac allografts survived, respectively. In conclusion, DST alone promotes a donor-specific infectious tolerance of a heart graft that can be adoptively transferred to subsequent naive allograft recipients despite the undiminished in vitro immunological response to donor Ag. Although both CD4+ and CD8+ populations are responsible for the regulatory mechanism in DST-induced tolerance, the CD4+ population appears to dominate.

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The Mechanism of the Induction of Immunologic Unresponsiveness to Rat Cardiac Allografts by Recipient Pretreatment With Donor Lymphocyte Subsets

Cited by 18 publications

References 0 publications

Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+ T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion

Anti-TCR-Specific DNA Vaccination Demonstrates a Role for a CD8+ T Cell Clone in the Induction of Allograft Tolerance by Donor-Specific Blood Transfusion

CD40Ig treatment results in allograft acceptance mediated by CD8+CD45RClow T cells, IFN-γ, and indoleamine 2,3-dioxygenase

Development of Infectious Tolerance After Donor-Specific Transfusion and Rat Heart Transplantation

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