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, Jahrgang 13, Nr. 8, 08.2013, S. 1963-75.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -