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Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen

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Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. / Gagliani, N; Jofra, T; Valle, A; Stabilini, A; Morsiani, C; Gregori, S; Deng, S; Rothstein, D M; Atkinson, M; Kamanaka, M; Flavell, R A; Roncarolo, M G; Battaglia, M.

In: AM J TRANSPLANT, Vol. 13, No. 8, 08.2013, p. 1963-75.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Gagliani, N, Jofra, T, Valle, A, Stabilini, A, Morsiani, C, Gregori, S, Deng, S, Rothstein, DM, Atkinson, M, Kamanaka, M, Flavell, RA, Roncarolo, MG & Battaglia, M 2013, 'Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen', AM J TRANSPLANT, vol. 13, no. 8, pp. 1963-75. https://doi.org/10.1111/ajt.12333

APA

Gagliani, N., Jofra, T., Valle, A., Stabilini, A., Morsiani, C., Gregori, S., Deng, S., Rothstein, D. M., Atkinson, M., Kamanaka, M., Flavell, R. A., Roncarolo, M. G., & Battaglia, M. (2013). Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. AM J TRANSPLANT, 13(8), 1963-75. https://doi.org/10.1111/ajt.12333

Vancouver

Gagliani N, Jofra T, Valle A, Stabilini A, Morsiani C, Gregori S et al. Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. AM J TRANSPLANT. 2013 Aug;13(8):1963-75. https://doi.org/10.1111/ajt.12333

Bibtex

@article{d642aea09d7345988bdd512e204bc4fd,
title = "Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen",
abstract = "The immune system is comprised of several CD4(+) T regulatory (Treg) cell types, of which two, the Foxp3(+) Treg and T regulatory type 1 (Tr1) cells, have frequently been associated with transplant tolerance. However, whether and how these two Treg-cell types synergize to promote allograft tolerance remains unknown. We previously developed a mouse model of allogeneic transplantation in which a specific immunomodulatory treatment leads to transplant tolerance through both Foxp3(+) Treg and Tr1 cells. Here, we show that Foxp3(+) Treg cells exert their regulatory function within the allograft and initiate engraftment locally and in a non-antigen (Ag) specific manner. Whereas CD4(+) CD25(-) T cells, which contain Tr1 cells, act from the spleen and are key to the maintenance of long-term tolerance. Importantly, the role of Foxp3(+) Treg and Tr1 cells is not redundant once they are simultaneously expanded/induced in the same host. Moreover, our data show that long-term tolerance induced by Foxp3(+) Treg-cell transfer is sustained by splenic Tr1 cells and functionally moves from the allograft to the spleen.",
keywords = "Adoptive Transfer, Animals, Antibodies, Monoclonal, CD4 Antigens, CD4-Positive T-Lymphocytes, Forkhead Transcription Factors, Graft Survival, Islets of Langerhans, Islets of Langerhans Transplantation, Leukocyte Common Antigens, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Spleen, T-Lymphocytes, Regulatory, Transplantation Tolerance, Transplantation, Homologous, Journal Article, Research Support, Non-U.S. Gov't",
author = "N Gagliani and T Jofra and A Valle and A Stabilini and C Morsiani and S Gregori and S Deng and Rothstein, {D M} and M Atkinson and M Kamanaka and Flavell, {R A} and Roncarolo, {M G} and M Battaglia",
note = "{\textcopyright} Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.",
year = "2013",
month = aug,
doi = "10.1111/ajt.12333",
language = "English",
volume = "13",
pages = "1963--75",
journal = "AM J TRANSPLANT",
issn = "1600-6135",
publisher = "Wiley-Blackwell",
number = "8",

}

RIS

TY - JOUR

T1 - Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen

AU - Gagliani, N

AU - Jofra, T

AU - Valle, A

AU - Stabilini, A

AU - Morsiani, C

AU - Gregori, S

AU - Deng, S

AU - Rothstein, D M

AU - Atkinson, M

AU - Kamanaka, M

AU - Flavell, R A

AU - Roncarolo, M G

AU - Battaglia, M

N1 - © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

PY - 2013/8

Y1 - 2013/8

N2 - The immune system is comprised of several CD4(+) T regulatory (Treg) cell types, of which two, the Foxp3(+) Treg and T regulatory type 1 (Tr1) cells, have frequently been associated with transplant tolerance. However, whether and how these two Treg-cell types synergize to promote allograft tolerance remains unknown. We previously developed a mouse model of allogeneic transplantation in which a specific immunomodulatory treatment leads to transplant tolerance through both Foxp3(+) Treg and Tr1 cells. Here, we show that Foxp3(+) Treg cells exert their regulatory function within the allograft and initiate engraftment locally and in a non-antigen (Ag) specific manner. Whereas CD4(+) CD25(-) T cells, which contain Tr1 cells, act from the spleen and are key to the maintenance of long-term tolerance. Importantly, the role of Foxp3(+) Treg and Tr1 cells is not redundant once they are simultaneously expanded/induced in the same host. Moreover, our data show that long-term tolerance induced by Foxp3(+) Treg-cell transfer is sustained by splenic Tr1 cells and functionally moves from the allograft to the spleen.

AB - The immune system is comprised of several CD4(+) T regulatory (Treg) cell types, of which two, the Foxp3(+) Treg and T regulatory type 1 (Tr1) cells, have frequently been associated with transplant tolerance. However, whether and how these two Treg-cell types synergize to promote allograft tolerance remains unknown. We previously developed a mouse model of allogeneic transplantation in which a specific immunomodulatory treatment leads to transplant tolerance through both Foxp3(+) Treg and Tr1 cells. Here, we show that Foxp3(+) Treg cells exert their regulatory function within the allograft and initiate engraftment locally and in a non-antigen (Ag) specific manner. Whereas CD4(+) CD25(-) T cells, which contain Tr1 cells, act from the spleen and are key to the maintenance of long-term tolerance. Importantly, the role of Foxp3(+) Treg and Tr1 cells is not redundant once they are simultaneously expanded/induced in the same host. Moreover, our data show that long-term tolerance induced by Foxp3(+) Treg-cell transfer is sustained by splenic Tr1 cells and functionally moves from the allograft to the spleen.

KW - Adoptive Transfer

KW - Animals

KW - Antibodies, Monoclonal

KW - CD4 Antigens

KW - CD4-Positive T-Lymphocytes

KW - Forkhead Transcription Factors

KW - Graft Survival

KW - Islets of Langerhans

KW - Islets of Langerhans Transplantation

KW - Leukocyte Common Antigens

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Spleen

KW - T-Lymphocytes, Regulatory

KW - Transplantation Tolerance

KW - Transplantation, Homologous

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/ajt.12333

DO - 10.1111/ajt.12333

M3 - SCORING: Journal article

C2 - 23834659

VL - 13

SP - 1963

EP - 1975

JO - AM J TRANSPLANT

JF - AM J TRANSPLANT

SN - 1600-6135

IS - 8

ER -