The Limits of Linked Suppression for Regulatory T cells
Background: We have previously found that CD4+CD25+ regulatory T cells (T regs) can adoptively transfer tolerance after its induction with co-stimulatory blockade in a mouse model of murine cardiac allograft transplantation. In these experiments, we tested an hypothesis with three components: 1) th...
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doaj-36ae159affd6473298adeeed6428fb972020-11-24T23:20:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242016-03-01710.3389/fimmu.2016.00082180742The Limits of Linked Suppression for Regulatory T cellsToshiro eIto0Akira eYamada1Ibrahim eBatal2Melissa Y Yeung3Martina eMcGrath4Mohamed H. Sayegh5Anil eChandraker6Takuya eUeno7Takuya eUeno8Massachusetts General Hospital, Harvard Medical SchoolMassachusetts General Hospital, Harvard Medical SchoolBrigham and Women's Hospital, Harvard Medical SchoolBrigham and Women's Hospital, Harvard Medical SchoolBrigham and Women's Hospital, Harvard Medical SchoolBrigham and Women's Hospital, Harvard Medical SchoolBrigham and Women's Hospital, Harvard Medical SchoolBrigham and Women's Hospital, Harvard Medical SchoolMassachusetts General Hospital, Harvard Medical SchoolBackground: We have previously found that CD4+CD25+ regulatory T cells (T regs) can adoptively transfer tolerance after its induction with co-stimulatory blockade in a mouse model of murine cardiac allograft transplantation. In these experiments, we tested an hypothesis with three components: 1) the T regs that transfer tolerance have the capacity for linked suppression, 2) the determinants that stimulate the T regs are expressed by the indirect pathway, and 3) the donor peptides contributing to these indirect determinants are derived from donor MHC antigens. Methods: 1st heart transplants were performed from the indicated donor strain to B10.D2 recipients along with co-stimulatory blockade treatment (250μg i.p. injection of MR1 on day 0 and 250μg i.p. injection of CTLA-4 Ig on day 2). At least 8 weeks later a 2nd heart transplant was performed to a new B10.D2 recipient that had been irradiated with 450 cGy. This recipient was given 40 x 106 naïve B10.D2 spleen cells plus 40 x 106 B10.D2 spleen cells from the first (tolerant) recipient. We performed 3 different types of heart transplants with using various donor.Results: 1. T regs suppress the graft rejection in an antigen-specific manner. 2. T regs generated in the face of MHC disparities suppress the rejection of grafts expressing third party MHC along with tolerant MHC. Conclusion:The limits of linkage appear to be quantitative and not universally determined by either the indirect pathway or by peptides of donor MHC antigens.http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00082/fulltoleranceregulatory T cellsCo-stimulationIndirect pathwayMHC class II |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Toshiro eIto Akira eYamada Ibrahim eBatal Melissa Y Yeung Martina eMcGrath Mohamed H. Sayegh Anil eChandraker Takuya eUeno Takuya eUeno |
spellingShingle |
Toshiro eIto Akira eYamada Ibrahim eBatal Melissa Y Yeung Martina eMcGrath Mohamed H. Sayegh Anil eChandraker Takuya eUeno Takuya eUeno The Limits of Linked Suppression for Regulatory T cells Frontiers in Immunology tolerance regulatory T cells Co-stimulation Indirect pathway MHC class II |
author_facet |
Toshiro eIto Akira eYamada Ibrahim eBatal Melissa Y Yeung Martina eMcGrath Mohamed H. Sayegh Anil eChandraker Takuya eUeno Takuya eUeno |
author_sort |
Toshiro eIto |
title |
The Limits of Linked Suppression for Regulatory T cells |
title_short |
The Limits of Linked Suppression for Regulatory T cells |
title_full |
The Limits of Linked Suppression for Regulatory T cells |
title_fullStr |
The Limits of Linked Suppression for Regulatory T cells |
title_full_unstemmed |
The Limits of Linked Suppression for Regulatory T cells |
title_sort |
limits of linked suppression for regulatory t cells |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2016-03-01 |
description |
Background: We have previously found that CD4+CD25+ regulatory T cells (T regs) can adoptively transfer tolerance after its induction with co-stimulatory blockade in a mouse model of murine cardiac allograft transplantation. In these experiments, we tested an hypothesis with three components: 1) the T regs that transfer tolerance have the capacity for linked suppression, 2) the determinants that stimulate the T regs are expressed by the indirect pathway, and 3) the donor peptides contributing to these indirect determinants are derived from donor MHC antigens. Methods: 1st heart transplants were performed from the indicated donor strain to B10.D2 recipients along with co-stimulatory blockade treatment (250μg i.p. injection of MR1 on day 0 and 250μg i.p. injection of CTLA-4 Ig on day 2). At least 8 weeks later a 2nd heart transplant was performed to a new B10.D2 recipient that had been irradiated with 450 cGy. This recipient was given 40 x 106 naïve B10.D2 spleen cells plus 40 x 106 B10.D2 spleen cells from the first (tolerant) recipient. We performed 3 different types of heart transplants with using various donor.Results: 1. T regs suppress the graft rejection in an antigen-specific manner. 2. T regs generated in the face of MHC disparities suppress the rejection of grafts expressing third party MHC along with tolerant MHC. Conclusion:The limits of linkage appear to be quantitative and not universally determined by either the indirect pathway or by peptides of donor MHC antigens. |
topic |
tolerance regulatory T cells Co-stimulation Indirect pathway MHC class II |
url |
http://journal.frontiersin.org/Journal/10.3389/fimmu.2016.00082/full |
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