Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease

Motoko Koyama; Rachel D. Kuns; Stuart D. Olver; Neil C. Raffelt; Yana A. Wilson; Alistair L.J. Don; Katie E. Lineburg; Melody Cheong; Renee J. Robb; Kate A. Markey; Antiopi Varelias; Bernard Malissen; Günter J. Hämmerling; Andrew D. Clouston; Christian R. Engwerda; Purnima Bhat; Kelli P.A. MacDonald; Geoffrey R. Hill

doi:10.1038/nm.2597

Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease

Motoko Koyama, Rachel D. Kuns, Stuart D. Olver, Neil C. Raffelt, Yana A. Wilson, Alistair L.J. Don, Katie E. Lineburg, Melody Cheong, Renee J. Robb, Kate A. Markey, Antiopi Varelias, Bernard Malissen, Günter J. Hämmerling, Andrew D. Clouston, Christian R. Engwerda, Purnima Bhat, Kelli P.A. MacDonald, Geoffrey R. Hill^*

^*Corresponding author for this work

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

193 Citations (Scopus)

Abstract

The presentation pathways by which allogeneic peptides induce graft-versus-host disease (GVHD) are unclear. We developed a bone marrow transplant (BMT) system in mice whereby presentation of a processed recipient peptide within major histocompatibility complex (MHC) class II molecules could be spatially and temporally quantified. Whereas donor antigen presenting cells (APCs) could induce lethal acute GVHD via MHC class II, recipient APCs were 100-1,000 times more potent in this regard. After myeloablative irradiation, T cell activation and memory differentiation occurred in lymphoid organs independently of alloantigen. Unexpectedly, professional hematopoietic-derived recipient APCs within lymphoid organs had only a limited capacity to induce GVHD, and dendritic cells were not required. In contrast, nonhematopoietic recipient APCs within target organs induced universal GVHD mortality and promoted marked alloreactive donor T cell expansion within the gastrointestinal tract and inflammatory cytokine generation. These data challenge current paradigms, suggesting that experimental lethal acute GVHD can be induced by nonhematopoietic recipient APCs.

Original language	English
Pages (from-to)	135-142
Number of pages	8
Journal	Nature Medicine
Volume	18
Issue number	1
DOIs	https://doi.org/10.1038/nm.2597
Publication status	Published - Jan 2012
Externally published	Yes

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Koyama, M., Kuns, R. D., Olver, S. D., Raffelt, N. C., Wilson, Y. A., Don, A. L. J., Lineburg, K. E., Cheong, M., Robb, R. J., Markey, K. A., Varelias, A., Malissen, B., Hämmerling, G. J., Clouston, A. D., Engwerda, C. R., Bhat, P., MacDonald, K. P. A., & Hill, G. R. (2012). Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease. Nature Medicine, 18(1), 135-142. https://doi.org/10.1038/nm.2597

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title = "Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease",

abstract = "The presentation pathways by which allogeneic peptides induce graft-versus-host disease (GVHD) are unclear. We developed a bone marrow transplant (BMT) system in mice whereby presentation of a processed recipient peptide within major histocompatibility complex (MHC) class II molecules could be spatially and temporally quantified. Whereas donor antigen presenting cells (APCs) could induce lethal acute GVHD via MHC class II, recipient APCs were 100-1,000 times more potent in this regard. After myeloablative irradiation, T cell activation and memory differentiation occurred in lymphoid organs independently of alloantigen. Unexpectedly, professional hematopoietic-derived recipient APCs within lymphoid organs had only a limited capacity to induce GVHD, and dendritic cells were not required. In contrast, nonhematopoietic recipient APCs within target organs induced universal GVHD mortality and promoted marked alloreactive donor T cell expansion within the gastrointestinal tract and inflammatory cytokine generation. These data challenge current paradigms, suggesting that experimental lethal acute GVHD can be induced by nonhematopoietic recipient APCs.",

author = "Motoko Koyama and Kuns, {Rachel D.} and Olver, {Stuart D.} and Raffelt, {Neil C.} and Wilson, {Yana A.} and Don, {Alistair L.J.} and Lineburg, {Katie E.} and Melody Cheong and Robb, {Renee J.} and Markey, {Kate A.} and Antiopi Varelias and Bernard Malissen and H{\"a}mmerling, {G{\"u}nter J.} and Clouston, {Andrew D.} and Engwerda, {Christian R.} and Purnima Bhat and MacDonald, {Kelli P.A.} and Hill, {Geoffrey R.}",

year = "2012",

month = jan,

doi = "10.1038/nm.2597",

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Koyama, M, Kuns, RD, Olver, SD, Raffelt, NC, Wilson, YA, Don, ALJ, Lineburg, KE, Cheong, M, Robb, RJ, Markey, KA, Varelias, A, Malissen, B, Hämmerling, GJ, Clouston, AD, Engwerda, CR, Bhat, P, MacDonald, KPA & Hill, GR 2012, 'Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease', Nature Medicine, vol. 18, no. 1, pp. 135-142. https://doi.org/10.1038/nm.2597

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AU - Koyama, Motoko

AU - Kuns, Rachel D.

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AU - Raffelt, Neil C.

AU - Wilson, Yana A.

AU - Don, Alistair L.J.

AU - Lineburg, Katie E.

AU - Cheong, Melody

AU - Robb, Renee J.

AU - Markey, Kate A.

AU - Varelias, Antiopi

AU - Malissen, Bernard

AU - Hämmerling, Günter J.

AU - Clouston, Andrew D.

AU - Engwerda, Christian R.

AU - Bhat, Purnima

AU - MacDonald, Kelli P.A.

AU - Hill, Geoffrey R.

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N2 - The presentation pathways by which allogeneic peptides induce graft-versus-host disease (GVHD) are unclear. We developed a bone marrow transplant (BMT) system in mice whereby presentation of a processed recipient peptide within major histocompatibility complex (MHC) class II molecules could be spatially and temporally quantified. Whereas donor antigen presenting cells (APCs) could induce lethal acute GVHD via MHC class II, recipient APCs were 100-1,000 times more potent in this regard. After myeloablative irradiation, T cell activation and memory differentiation occurred in lymphoid organs independently of alloantigen. Unexpectedly, professional hematopoietic-derived recipient APCs within lymphoid organs had only a limited capacity to induce GVHD, and dendritic cells were not required. In contrast, nonhematopoietic recipient APCs within target organs induced universal GVHD mortality and promoted marked alloreactive donor T cell expansion within the gastrointestinal tract and inflammatory cytokine generation. These data challenge current paradigms, suggesting that experimental lethal acute GVHD can be induced by nonhematopoietic recipient APCs.

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JO - Nature Medicine

JF - Nature Medicine

IS - 1

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Recipient nonhematopoietic antigen-presenting cells are sufficient to induce lethal acute graft-versus-host disease

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