Allograft Tolerance Induction in Adult Mice Associated With Functional Deletion of Specific CTL Precursors

Twuyver, E. van; Kast, W. Martin; Mooijaart, R. J. D.; Wilmink, J. M.; Melief, C. J. M.; Waal, L. P. de

doi:10.1097/00007890-198911000-00024

Cited by 26 publications

(8 citation statements)

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“…We and others have demonstrated that pre-transplant infusion of single MHC class I locus-mismatched lymphocytes from allograft donors leads to significant prolongation of donor-specific skin graft survival [6][7][8][9][10]12]. It was also shown that anti-donor CD8 + T cell were eliminated after DLI [7][8][9], and that regulatory T cells may be involved in DLI-induced donor-specific transplantation tolerance [12,37]. However, the mechanism by which regulatory T cells mediate antigen-specific suppression remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…However, the molecular mechanisms by which regulatory T cells exert their function remain unclear. Previous studies have demonstrated that single MHC class I locus mismatched pre-transplantation donor-lymphocyte infusion (DLI) can enhance donor-specific allograft survival [6][7][8][9][10]. Because none of the recipients were thymectomized, the function of newly released anti-donor T cells from the thymus must have been inhibited to maintain the allografts.…”

Section: Introductionmentioning

confidence: 99%

“…Because none of the recipients were thymectomized, the function of newly released anti-donor T cells from the thymus must have been inhibited to maintain the allografts. Indeed, alloantigen reactive CD8 + T cells are inhibited [7][8][9]11]. We have demonstrated that double negative (DN) regulatory T cells are able to specifically suppress anti-donor CD8 + T cells in vitro and in vivo by eliminating activated syngeneic CD8 + T cells through direct cell-cell contact [12].…”

Section: Introductionmentioning

confidence: 99%

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Ly-6A is critical for the function of double negative regulatory T cells

2002

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We have recently demonstrated that CD3+CD4–CD8– double negative (DN) T cells can down‐regulate allogeneic immune responses both in vitro and in vivo by killing activated syngeneic CD8+ T cells. The goal of this study was to identify molecules that are crucial for DN T cell‐mediated suppression. We demonstrate that Ly‐6A (Sca‐1) is highly expressed on DN T cells. Incubation with IL‐10 significantly reduced Ly‐6A expression and the function of DN T cells. DN T cell‐mediated killing was significantly reduced when Ly‐6A was blocked.Ly‐6A‐deficient mice showed an accelerated allograft rejection when compared to wild‐type controls. Furthermore we demonstrate that pretransplantation donor lymphocyte infusion (DLI) led to activation and proliferation of recipient DN T cells and prolongation of bm1→B6 skin allograft survival. However, when the recipients were deficient in Ly‐6A, the beneficial effect of DLI on allograftsurvival was abolished. Moreover, deficiency in Ly‐6A did not affect the activation and proliferation of DN T cells. Rather, it impaired the ability of DN T cells to kill activated anti‐donor CD8+ Tcells. Taken together, our data indicate that Ly‐6A plays a crucial role in DN T cell‐mediated regulation in vitro and in vivo, perhaps by enhancing DN‐CD8+ T cell signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ly-6A is critical for the function of double negative regulatory T cells

2002

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“…Thus, in the almost 200 patients studied, graft survival was better, alloantibody formation less, and mixed lymphocyte culture (MLC) and cytotoxic reactivity remained unchanged when blood transfusion donor and recipient shared a single HLA-DR antigen (19). Preliminary data of van Twuyver, de Waal, and others show a significant decrease in cytotoxic T cell precursor (CTLp) frequency in five recipients after transfusion of blood from an unrelated donor who shared one HLA haplotype with the respective recipient (21). Against a third party, the CTLp frequency remained the same.…”

Section: Historical Perspectivementioning

confidence: 99%

The Influence of Allogeneic Cells on the Human T and B Cell Repertoire

Rood

Claas

1990

Science

106

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Clinical transplantation is often complicated by rejection episodes, in which the immune system of the recipient reacts to the foreign transplantation (HLA) antigens on the graft. This immune response includes humoral and cellular components. In the first, B lymphocytes form antibodies to the HLA alloantigens. In the second, CD8+ T lymphocytes recognize and react to HLA class I antigens, and CD4+ T cells react to HLA class II antigens. The frequency and severity of these rejection episodes can be diminished by immunosuppressive drugs, HLA matching between donor and recipient, and immune modulation by blood transfusion. Effective HLA matching between donor and recipient is not always possible and often not necessary. Insight into the factors that influence the T and B cell repertoire after blood transfusion might lead to new approaches to improve graft survival.

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“…injection of allogeneic SC across an H-2 class I1 disparity leads to specific skin allograft enhancement. Similarly, as was shown before, specific allograft tolerance can be obtained across an H-2 class1 disparity [13,14,171. In contrast, i.v.…”

Section: Discussionmentioning

confidence: 61%

Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H‐2 class II mismatch. Different mechanisms operate in tolerization across an H‐2 class I vs. H‐2 class II disparity

Twuyver¹,

Kast²,

Mooijaart³

et al. 1990

Eur J Immunol

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Previously, we have shown that the intravenous (i.v.) injection of allogeneic lymphocytes across an H-2 class I-mutant disparity leads to specific skin allograft tolerance caused by irradiation-sensitive donor T cells, which function as veto cells. In the present study, we show that the i.v. injection of H-2 class II-incompatible spleen cells also results in specific skin allograft tolerance. However, tolerance induction depends on the presence of irradiation-resistant non-T cells in the donor cell inoculum. Thus, different mechanisms operate in tolerance induction across an H-2 class I vs. H-2 class II mismatch. I.v. injection of allogeneic spleen cells across an H-2 class I plus class II disparity does not result in skin allograft tolerance. Finally, our data show that transfusion-induced suppression of the delayed-type hypersensitivity response against alloantigens does not correlate with skin allograft tolerance induced by i.v. injected allogeneic lymphocytes. In conclusion, the type of H-2 mismatch between transfusion donor and recipient not only determines the occurrence of allograft tolerance but also the mechanism leading to tolerization.

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Allograft Tolerance Induction in Adult Mice Associated With Functional Deletion of Specific CTL Precursors

Cited by 26 publications

References 0 publications

Ly-6A is critical for the function of double negative regulatory T cells

Ly-6A is critical for the function of double negative regulatory T cells

The Influence of Allogeneic Cells on the Human T and B Cell Repertoire

Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H‐2 class II mismatch. Different mechanisms operate in tolerization across an H‐2 class I vs. H‐2 class II disparity

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