Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells

Chaorui Tian; Xueli Yuan; Jessamyn Bagley; Bruce R. Blazar; Mohamed H. Sayegh; John Iacomini

doi:10.1016/j.clim.2008.01.005

Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells

Chaorui Tian, Xueli Yuan, Jessamyn Bagley, Bruce R. Blazar, Mohamed H. Sayegh, John Iacomini

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The observation that bone marrow derived hematopoietic cells are potent inducers of tolerance has generated interest in trying to establish transplantation tolerance by inducing a state of hematopoietic chimerism through allogeneic bone marrow transplantation. However, this approach is associated with serious complications that limit its utility for tolerance induction. Here we describe the development of a novel approach that allows for tolerance induction without the need for an allogeneic bone marrow transplant by combining non-myeloablative host conditioning with delivery of donor alloantigen by adoptively transferred T cells. CBA/Ca mice were administered 2.5 Gy whole body irradiation (WBI). The following day the mice received K^b disparate T cells from MHC class I transgenic CBK donor mice, as well as rapamycin on days 0-13 and anti-CD40L monoclonal antibody on days 0-5, 8, 11 and 14 relative to T cell transfer. Mice treated using this approach were rendered specifically tolerant to CBK skin allografts through a mechanism involving central and peripheral deletion of alloreactive T cells. These data suggest robust tolerance can be established without the need for bone marrow transplantation using clinically relevant non-myeloablative conditioning combined with antigen delivery by T cells.

Original language	English (US)
Pages (from-to)	130-137
Number of pages	8
Journal	Clinical Immunology
Volume	127
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2008.01.005
State	Published - May 2008

Bibliographical note

Funding Information:
We wish to thank members of the Iacomini and Sayegh laboratories for their helpful suggestions. C.T. is supported by an American Society of Transplantation (AST)/Roche Basic Science Faculty Development Grant. This work was supported by National Institutes of Health Grants P01 AI041521 and P01 AI056299 to M.H.S; R01 AI043619, R01 AI053666 and R01 AI070601 to J.I.; and R01 HL63452 and P01 AI056299 to BRB. Support for this work was also provided to M.H.S. by The Juvenile Diabetes Research Foundation Center Grant on Immunological Tolerance in Type I Diabetes, and to J.I. by the American Diabetes Association 7-04-RA-45.

Keywords

Negative selection
Non-myeloablative conditioning
T cells
Tolerance
Transplantation

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title = "Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells",

abstract = "The observation that bone marrow derived hematopoietic cells are potent inducers of tolerance has generated interest in trying to establish transplantation tolerance by inducing a state of hematopoietic chimerism through allogeneic bone marrow transplantation. However, this approach is associated with serious complications that limit its utility for tolerance induction. Here we describe the development of a novel approach that allows for tolerance induction without the need for an allogeneic bone marrow transplant by combining non-myeloablative host conditioning with delivery of donor alloantigen by adoptively transferred T cells. CBA/Ca mice were administered 2.5 Gy whole body irradiation (WBI). The following day the mice received Kb disparate T cells from MHC class I transgenic CBK donor mice, as well as rapamycin on days 0-13 and anti-CD40L monoclonal antibody on days 0-5, 8, 11 and 14 relative to T cell transfer. Mice treated using this approach were rendered specifically tolerant to CBK skin allografts through a mechanism involving central and peripheral deletion of alloreactive T cells. These data suggest robust tolerance can be established without the need for bone marrow transplantation using clinically relevant non-myeloablative conditioning combined with antigen delivery by T cells.",

keywords = "Negative selection, Non-myeloablative conditioning, T cells, Tolerance, Transplantation",

author = "Chaorui Tian and Xueli Yuan and Jessamyn Bagley and Blazar, {Bruce R.} and Sayegh, {Mohamed H.} and John Iacomini",

note = "Funding Information: We wish to thank members of the Iacomini and Sayegh laboratories for their helpful suggestions. C.T. is supported by an American Society of Transplantation (AST)/Roche Basic Science Faculty Development Grant. This work was supported by National Institutes of Health Grants P01 AI041521 and P01 AI056299 to M.H.S; R01 AI043619, R01 AI053666 and R01 AI070601 to J.I.; and R01 HL63452 and P01 AI056299 to BRB. Support for this work was also provided to M.H.S. by The Juvenile Diabetes Research Foundation Center Grant on Immunological Tolerance in Type I Diabetes, and to J.I. by the American Diabetes Association 7-04-RA-45.",

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AU - Sayegh, Mohamed H.

AU - Iacomini, John

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Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells

Abstract

Bibliographical note

Keywords

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