ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease

doi:10.1126/scitranslmed.aab0166

. 2015 Oct 7;7(308):308ra160.

doi: 10.1126/scitranslmed.aab0166.

ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease

Affiliations

¹ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
² Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA.
³ Department of Pathology and Immunology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
⁴ Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁵ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA.
⁷ Department of Hematology/Oncology, Mie University Hospital, Mie 514-8507, Japan.
⁸ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA. sophpacz@iu.edu.

PMID: 26446957
PMCID: PMC4699312
DOI: 10.1126/scitranslmed.aab0166

ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease

Jilu Zhang et al. Sci Transl Med. 2015.

. 2015 Oct 7;7(308):308ra160.

doi: 10.1126/scitranslmed.aab0166.

Authors

Affiliations

¹ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
² Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN 46202, USA.
³ Department of Pathology and Immunology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
⁴ Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁵ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN 55454, USA.
⁷ Department of Hematology/Oncology, Mie University Hospital, Mie 514-8507, Japan.
⁸ Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Melvin and Bren Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA. sophpacz@iu.edu.

PMID: 26446957
PMCID: PMC4699312
DOI: 10.1126/scitranslmed.aab0166

Abstract

Graft-versus-host disease (GVHD) remains a devastating complication after allogeneic hematopoietic cell transplantation (HCT). We previously identified high plasma soluble suppression of tumorigenicity 2 (sST2) as a biomarker of the development of GVHD and death. sST2 sequesters interleukin-33 (IL-33), limiting its availability to T cells expressing membrane-bound ST2 (mST2) [T helper 2 (TH2) cells and ST2(+)FoxP3(+) regulatory T cells]. We report that blockade of sST2 in the peritransplant period with a neutralizing monoclonal antibody (anti-ST2 mAb) reduced GVHD severity and mortality. We identified intestinal stromal cells and T cells as major sources of sST2 during GVHD. ST2 blockade decreased systemic interferon-γ, IL-17, and IL-23 but increased IL-10 and IL-33 plasma levels. ST2 blockade also reduced sST2 production by IL-17-producing T cells while maintaining protective mST2-expressing T cells, increasing the frequency of intestinal myeloid-derived suppressor cells, and decreasing the frequency of intestinal CD103 dendritic cells. Finally, ST2 blockade preserved graft-versus-leukemia activity in a model of green fluorescent protein (GFP)-positive MLL-AF9 acute myeloid leukemia. Our findings suggest that ST2 is a therapeutic target for severe GVHD and that the ST2/IL-33 pathway could be investigated in other T cell-mediated immune disorders with loss of tolerance.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest:

Dr. Paczesny has a patent on “Methods of detection of graft-versus-host disease” licensed to Viracor-IBT Laboratories. Otherwise, the authors have no other relevant conflicts of interest to declare.

Figures

**Fig. 1. ST2 blockade and GVHD**
(A) Irradiated C3H.SW mice (1100 cGy) were transplanted with syngeneic ( ) or allogeneic B6 ( ) BM cells (5 × 10⁶) and splenic purified T cells (2 × 10⁶). Soluble ST2 concentrations in plasma collected at indicated times post-HCT from C3H.SW recipients (unit: ng/mL) (p=0.0001; n=10–12; t-test). The data are from 4 independent experiments. (B) Clinical scores of GVHD and survival curves for C3H.SW mice receiving syngeneic ( ) or allogeneic B6 cells and treated with anti-mouse ST2 antibody ( ) or IgG control antibody ( ) at day -1 and day +1 post-HCT. The data are from 3 independent experiments (p values for GVHD scores are in Table S1, p=0.0256 for survival analysis; n=15–23 per group; t-test for GVHD score and Log-rank test for survival analysis). (C) Irradiated NSG mice (350 cGy) received 2.5 × 10⁶ T cells purified from PBMCs of healthy donors ( ). The control group was irradiated without receiving human T cells ( ). Human soluble ST2 concentrations in plasma collected at indicated times post-HCT from NSG recipient mice with or without engrafted human T cells (unit: pg/mL). The data are from 3 independent experiments (p=0.0028; n=7–9 per group; t-test). (D) Clinical scores of GVHD and survival curves for NSG mice receiving human T cells and treated with anti-human and anti-mouse ST2 antibodies ( ) or IgG control antibody ( ) every other day from day -1 to day +5 (4 doses) (p values for GVHD scores are in Table S1, p= 0.0329 for survival analysis; n=10 per group; t-test for GVHD score and Log-rank test for survival analysis). (E) IFN-γ, IL-17, IL-23, IL-10, and IL-33 concentrations in plasma collected every 5 days post-HCT from the B6→C3H.SW model (unit: pg/mL). The data are from 3 independent experiments. Syngeneic group ( ); allogeneic groups treated with anti-ST2 ( ) or IgG control ( ) (p values are in Table S1; n=3–9 per group, t-test).

formula image — **Fig. 1. ST2 blockade and GVHD**
(A) Irradiated C3H.SW mice (1100 cGy) were transplanted with syngeneic ( ) or allogeneic B6 ( ) BM cells (5 × 10⁶) and splenic purified T cells (2 × 10⁶). Soluble ST2 concentrations in plasma collected at indicated times post-HCT from C3H.SW recipients (unit: ng/mL) (p=0.0001; n=10–12; t-test). The data are from 4 independent experiments. (B) Clinical scores of GVHD and survival curves for C3H.SW mice receiving syngeneic ( ) or allogeneic B6 cells and treated with anti-mouse ST2 antibody ( ) or IgG control antibody ( ) at day -1 and day +1 post-HCT. The data are from 3 independent experiments (p values for GVHD scores are in Table S1, p=0.0256 for survival analysis; n=15–23 per group; t-test for GVHD score and Log-rank test for survival analysis). (C) Irradiated NSG mice (350 cGy) received 2.5 × 10⁶ T cells purified from PBMCs of healthy donors ( ). The control group was irradiated without receiving human T cells ( ). Human soluble ST2 concentrations in plasma collected at indicated times post-HCT from NSG recipient mice with or without engrafted human T cells (unit: pg/mL). The data are from 3 independent experiments (p=0.0028; n=7–9 per group; t-test). (D) Clinical scores of GVHD and survival curves for NSG mice receiving human T cells and treated with anti-human and anti-mouse ST2 antibodies ( ) or IgG control antibody ( ) every other day from day -1 to day +5 (4 doses) (p values for GVHD scores are in Table S1, p= 0.0329 for survival analysis; n=10 per group; t-test for GVHD score and Log-rank test for survival analysis). (E) IFN-γ, IL-17, IL-23, IL-10, and IL-33 concentrations in plasma collected every 5 days post-HCT from the B6→C3H.SW model (unit: pg/mL). The data are from 3 independent experiments. Syngeneic group ( ); allogeneic groups treated with anti-ST2 ( ) or IgG control ( ) (p values are in Table S1; n=3–9 per group, t-test).

**Fig. 2. Soluble ST2 (sST2) and membrane ST2 (mST2) expression during GVHD**
(A) In the B6→C3H.SW model, mRNA expression of sST2 and mST2 in different organs (spleen, small intestine, large intestine, skin, bone marrow, lung, heart, liver, and peripheral blood) of C3H.SW recipients mice at day 10 post-allogeneic HCT. The data are from 4 independent experiments (p values are in Table S2; n=4; one-way ANOVA). (B) sST2/actin mRNA expression in intestine or intestinal cell subsets (epithelial cells, stromal cells, endothelial cells, or non-T hematopoietic cells) from C3H.SW recipients mice at day 10 post-allogeneic HCT (n=5). The data are from 2 independent experiments with 2–3 pooled mice. (C) Western blot analysis of sorted intestinal stromal cells from IgG control or anti-ST2 antibody treated C3H.SW recipients mice at day 10 post-allogeneic HCT [M=marker (kDa)] (left). The red box indicates the lack of sST2 protein present after anti-ST2 treatment. The bar graph shows the sST2/actin ratio in IgG control or anti-ST2 treated mice (n=6). The data are from 2 independent experiments with 3 pooled mice. (D) sST2/actin expression on sorted intestinal stromal cells and T cells from C3H.SW mice at day 10 and day 28 post-allogeneic HCT. The data are from 2 independent experiments with 2–3 pooled mice (p=0.0120; n=5; t-test). (E) Western blot analysis of sorted intestinal T cells from IgG control or anti-ST2 antibody–treated C3H.SW recipients 10 days post-allogeneic HCT [M=marker (kDa)]. The red box indicates the lack of sST2 protein present after anti-ST2 treatment. The unmodified blots are in Fig. S9. The bar graph shows the sST2/actin ratio in CD4 T cells from IgG control or anti-ST2 treated mice. The data are from 2 independent experiments with 3 pooled mice (p=0.0032; n=6; t-test). (F) sST2 secretion by both murine and human in vitro differentiated T cell subsets. The data are from 3–4 independent experiments (p values are in Table S2; n=3–4; t-test). The unmodified blots are in Fig. S9.

**Fig. 3. ST2 deficiency and T cell populations during GVHD**
(A) Transcriptome analysis of T cell related genes in mesenteric lymph node (MLN) T cells from anti-ST2–treated vs. IgG–treated C3H.SW recipient mice at day 10 post-allogeneic HCT. MLN T cells from 4 mice in each group were pooled for analysis. (B and C) Flow cytometric analysis of transcription factor and cytokine production by donor-derived CD4+ splenic T cells from IgG-treated or anti-ST2-treated C3H.SW recipients mice at day 10 after allogeneic HCT. The bar graphs show the percentages of cells expressing IFN-γ or Tbet (p=0.0150 for IFN-γ, p=0.0055 for T-bet; n=5; t-test) (B) and IL-17/IFN-γ or RORγt (p= 0.0003 for IL-17/IFN-γ and p=0.0075 for RORγt; n=4–5; t-test) (C). The data are from 2 independent experiments. Gating strategy for (B) and (C) found in Fig. S10. (D) Survival curves for C3H.SW recipient mice receiving either only 5 × 10⁶ wild type (WT) B6 BM cells ( ) or 2 × 10⁶ WT ( ) or ST2^−/− B6 T cells ( ) (p=0.0289; n=6–10; Log-rank test). The data are from 2 independent experiments. (E–G) Flow cytometric analysis at day 10 after allogeneic HCT shows percentages of intestinal CD4+ T cells expressing IFN-γ and Tbet (p=0.0173 for IFN-γ and p=0.0320 for Tbet; n=4; t-test) (E) and IL-17/IFN-γ, and RORγt (p=0.0273 for IL-17/IFN-γ and p=0.0273 for RORγt; n=4–5; t-test) (F) as well as Ki67 proliferation staining of cells expressing both IL-17 and IFN-γ (p=0.0088; n=4; t-test) (G). The data are from 2 independent experiments. (H) The bar graphs show the percentages of T cells expressing IL-4 or GATA3 from IgG-treated or anti-ST2-treated C3H.SW recipients mice at day 10 after allogeneic HCT, and the flow cytometry plots show mST2 expression on GATA3 T cells after IgG or anti-ST2 treatment. The data are from 2 independent experiments (p=0.0049 for IL-4 and p=0.0252 for GATA3; n=6; t-test). (I) IL-4 and GATA3-expressing T cells from C3H.SW recipient mice receiving WT or ST2^−/− B6 T cells at day 10 after allogeneic HCT (p=0.0032 for IL-4 and p=0.0253 for GATA3; n=4; t-test). The data are from 2 independent experiments. (J) The bar graphs show the percentages of intestinal T cells expressing FoxP3 from IgG-treated or anti-ST2-treated C3H.SW recipients mice at day 10 after allogeneic HCT, and the flow cytometry plots show mST2 expression on FoxP3 T cells after IgG or anti-ST2 treatment (p=0.0087; n=5; t-test). The data are from 2 independent experiments. (K) FoxP3 and IL-10 expressing T cells from C3H.SW recipient mice receiving WT or ST2^−/− B6 T cells at day 10 after allogeneic HCT. The data are from 2 independent experiments (p=0.0459 for FoxP3 and p=0.0471 for IL-10; n=4–5; t-test). (L) Survival curves for C3H.SW recipients mice transplanted with 5 × 10⁶ B6 TCD BM cells plus either 2 × 10⁵ WT ( ) or ST2^−/− B6 ( ) regulatory T cells (Tregs) with 2 × 10⁶ WT B6 conventional T cells. ( TCD BM only). The data are from 2 independent experiments (p=0.043; n=5–10 per group; Log-rank test). Flow cytometric gating strategies are in Fig. S10.

**Fig. 4. ST2 deficiency and antigen-presenting cells during GVHD**
Flow cytometric analysis of intestinal myeloid-derived suppressor cells (MDSCs = MAC-1⁺Gr-1⁺ cells), CD103⁺ dendritic cells, and CD11c⁺ total dendritic cells in the B6 (CD45.1⁺)→C3H.SW (CD45.2⁺) model at 10 days post-allogeneic HCT. (A) Donor CD45.1⁺ MDSCs in IgG control or anti-ST2-treated C3H.SW recipients (p=0.0247; n=4; t-test). The data are from 2 independent experiments. (B) Donor CD45.1⁺ MDSCs in C3H.SW recipients receiving WT or ST2^−/− B6 T cells (p=0.0277; n=3; t-test). (C) Donor CD45.1⁺CD103⁺ dendritic cells in IgG control or anti-ST2-treated C3H.SW recipients (p=0.0012; n=8; t-test). The data are from 4 independent experiments. (D) Donor CD45.1⁺CD103⁺ dendritic cells in C3H.SW recipients receiving WT or ST2^−/− B6 T cells (p=0.0244; n=3; t-test). **(E)** Expression of MHC-II and co-stimulation molecules on CD11c⁺ total dendritic cells from IgG control and anti-ST2-treated mice, representative flow cytometry histograms (top panels) and bar graphs (bottom panels) of mean fluorescence intensity (MFI) (p=0.0391 for MHC II, p=0.0469 for CD40, p=0.0154 for CD80, and p=0.0263 for CD86; n=3; t-test). Flow cytometric gating strategies are in Fig. S11.

**Fig. 5. ST2 deficiency and GVL activity**
(A) Transcriptome analysis of anti-tumor related genes in MLN T cells from anti-ST2-treated vs. IgG-treated C3H.SW recipient mice at day 10 post-allogeneic HCT. MLN T cells from 4 mice in each group were pooled for analysis. (B) In vitro cytotoxic T lymphocyte assay with A20 and MLL-AF9 retrovirally induced acute myeloid leukemia in the presence of IgG control and anti-ST2 mAb (5 μg/mL) (n=3). The data are from 3 independent experiments. (C) Survival curves of C3H.SW mice receiving 10⁴ GFP⁺ MLL-AF9 leukemic cells with syngeneic HCT C3H.SW→C3H.SW ( ) or allogeneic HCT (B6→C3H.SW) treated with IgG control ( ) or anti-ST2 mAb ( ) (p=0.010; n=5–10 per group; Log-rank test). (D) Survival curves of C3H.SW mice receiving 10⁴ GFP⁺ MLL-AF9 leukemic cells with syngeneic HCT C3H.SW→C3H.SW ( ) or allogeneic HCT (B6→C3H.SW) treated with 6 doses (100 μg/dose, every other day from day -1 to day +9) of IgG control ( ) or anti-ST2 mAb ( ) (p=0.0357; n=4–5 per group; Log-rank test). (E) Survival curves of C3H.SW mice receiving 10⁴ GFP⁺ MLL-AF9 leukemic cells with WT ( ) or ST2^−/− ( ) B6 T cells (p=0.0203; n=6–10 per group; Log-rank test).

See this image and copyright information in PMC

Comment in

The emerging role of sST2 blocking in the therapy of graft-versus-host disease.
Xiao Y, Zheng F. Xiao Y, et al. Ann Transl Med. 2016 Oct;4(Suppl 1):S42. doi: 10.21037/atm.2016.10.22. Ann Transl Med. 2016. PMID: 27868010 Free PMC article. No abstract available.
Prospects to translate the biology of IL-33 and ST2 during organ transplantation into therapeutics to treat graft-versus-host disease.
Scott IC, Houslay KF, Cohen ES. Scott IC, et al. Ann Transl Med. 2016 Dec;4(24):500. doi: 10.21037/atm.2016.11.74. Ann Transl Med. 2016. PMID: 28149862 Free PMC article. No abstract available.

Cited by

Early inflammatory markers as prognostic indicators following allogeneic stem cell transplantation.
Verma K, Croft W, Greenwood D, Stephens C, Malladi R, Nunnick J, Zuo J, Kinsella FAM, Moss P. Verma K, et al. Front Immunol. 2024 Jan 3;14:1332777. doi: 10.3389/fimmu.2023.1332777. eCollection 2023. Front Immunol. 2024. PMID: 38235129 Free PMC article.
Biomarker Panel for Chronic Graft-Versus-Host Disease.
Yu J, Storer BE, Kushekhar K, Abu Zaid M, Zhang Q, Gafken PR, Ogata Y, Martin PJ, Flowers ME, Hansen JA, Arora M, Cutler C, Jagasia M, Pidala J, Hamilton BK, Chen GL, Pusic I, Lee SJ, Paczesny S. Yu J, et al. J Clin Oncol. 2016 Aug 1;34(22):2583-90. doi: 10.1200/JCO.2015.65.9615. Epub 2016 May 23. J Clin Oncol. 2016. PMID: 27217465 Free PMC article.
Tissue Cytokine IL-33 Modulates the Cytotoxic CD8 T Lymphocyte Activity During Nutrient Deprivation by Regulation of Lineage-Specific Differentiation Programs.
Dreis C, Ottenlinger FM, Putyrski M, Ernst A, Huhn M, Schmidt KG, Pfeilschifter JM, Radeke HH. Dreis C, et al. Front Immunol. 2019 Jul 24;10:1698. doi: 10.3389/fimmu.2019.01698. eCollection 2019. Front Immunol. 2019. PMID: 31396219 Free PMC article.
IL-33 Augments Virus-Specific Memory T Cell Inflation and Potentiates the Efficacy of an Attenuated Cytomegalovirus-Based Vaccine.
McLaren JE, Clement M, Marsden M, Miners KL, Llewellyn-Lacey S, Grant EJ, Rubina A, Gimeno Brias S, Gostick E, Stacey MA, Orr SJ, Stanton RJ, Ladell K, Price DA, Humphreys IR. McLaren JE, et al. J Immunol. 2019 Feb 1;202(3):943-955. doi: 10.4049/jimmunol.1701757. J Immunol. 2019. PMID: 30635396 Free PMC article.
Extracorporeal Photopheresis (ECP) and the Potential of Novel Biomarkers in Optimizing Management of Acute and Chronic Graft vs. Host Disease (GvHD).
Mankarious M, Matthews NC, Snowden JA, Alfred A. Mankarious M, et al. Front Immunol. 2020 Jan 31;11:81. doi: 10.3389/fimmu.2020.00081. eCollection 2020. Front Immunol. 2020. PMID: 32082329 Free PMC article. Review.

See all "Cited by" articles

References

1. Wu CJ, Ritz J. Induction of tumor immunity following allogeneic stem cell transplantation. Adv Immunol. 2006;90:133–173. - PubMed
1. Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112:4371–4383. - PubMed
1. Warren EH, Deeg HJ. Dissecting graft-versus-leukemia from graft-versus-host-disease using novel strategies. Tissue antigens. 2013;81:183–193. - PMC - PubMed
1. Shlomchik WD. Graft-versus-host disease. Nature reviews Immunology. 2007;7:340–352. - PubMed
1. Markey KA, MacDonald KP, Hill GR. The biology of graft-versus-host disease: experimental systems instructing clinical practice. Blood. 2014 - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
Research Materials
- NCI CPTC Antibody Characterization Program

[1] Wu CJ, Ritz J. Induction of tumor immunity following allogeneic stem cell transplantation. Adv Immunol. 2006;90:133–173. - PubMed

[2] Wu CJ, Ritz J. Induction of tumor immunity following allogeneic stem cell transplantation. Adv Immunol. 2006;90:133–173. - PubMed

[3] Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112:4371–4383. - PubMed

[4] Kolb HJ. Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood. 2008;112:4371–4383. - PubMed

[5] Warren EH, Deeg HJ. Dissecting graft-versus-leukemia from graft-versus-host-disease using novel strategies. Tissue antigens. 2013;81:183–193. - PMC - PubMed

[6] Warren EH, Deeg HJ. Dissecting graft-versus-leukemia from graft-versus-host-disease using novel strategies. Tissue antigens. 2013;81:183–193. - PMC - PubMed

[7] Shlomchik WD. Graft-versus-host disease. Nature reviews Immunology. 2007;7:340–352. - PubMed

[8] Shlomchik WD. Graft-versus-host disease. Nature reviews Immunology. 2007;7:340–352. - PubMed

[9] Markey KA, MacDonald KP, Hill GR. The biology of graft-versus-host disease: experimental systems instructing clinical practice. Blood. 2014 - PMC - PubMed

[10] Markey KA, MacDonald KP, Hill GR. The biology of graft-versus-host disease: experimental systems instructing clinical practice. Blood. 2014 - PMC - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease

Affiliations

ST2 blockade reduces sST2-producing T cells while maintaining protective mST2-expressing T cells during graft-versus-host disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials

Abstract

Conflict of interest statement

Figures

Comment in

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials