ArticleBlood2010
GVHD after haploidentical transplantation: a novel, MHC-defined rhesus macaque model identifies CD28- CD8+ T cells as a reservoir of breakthrough T-cell proliferation during costimulation blockade and sirolimus-based immunosuppression.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 79 citations in OpenAlex.
- Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Animal models of chronic graft-versus-host disease with oral involvement: A review.European journal of oral sciences · 2026Review
- Article
- Biochemical and hematological reference intervals in rhesus and cynomolgus macaques and implications for vaccine and drug development.Lab animal · 2025Article
- Targeting cell-surface VISTA expression on allospecific naïve T cells promotes tolerance.Blood · 2025Article
- Organ-specific microenvironments drive divergent T cell evolution in acute graft-versus-host disease.Science translational medicine · 2025Article
- Article
- Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD.Blood advances · 2023Article
- Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse.Science translational medicine · 2023Article
- Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.Immunity · 2023Article
- Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates.Science translational medicine · 2023Article
- Abatacept GVHD prophylaxis in unrelated hematopoietic cell transplantation for pediatric bone marrow failure.Blood advances · 2023Article
- Article
- Role of abatacept in the prevention of graft-Therapeutic advances in hematology · 2023Review
- Treg in inborn errors of immunity: gaps, knowns and future perspectives.Frontiers in immunology · 2023Review
- Graft-versus-host disease: teaching old drugs new tricks at less cost.Frontiers in immunology · 2023Review
- Allogeneic MHC-matched T-cell receptor α/β-depleted bone marrow transplants in SHIV-infected, ART-suppressed Mauritian cynomolgus macaques.Scientific reports · 2022Article
- Single-Cell-Based High-Throughput Ig and TCR Repertoire Sequencing Analysis in Rhesus Macaques.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Milestones in acute GVHD pathophysiology.Frontiers in immunology · 2022Review
- Insights from integrating clinical and preclinical studies advance understanding of graft-versus-host disease.The Journal of clinical investigation · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 4 institutions in 1 country.
Funding
Abstract
We have developed a major histocompatibility complex-defined primate model of graft-versus-host disease (GVHD) and have determined the effect that CD28/CD40-directed costimulation blockade and sirolimus have on this disease. Severe GVHD developed after haploidentical transplantation without prophylaxis, characterized by rapid clinical decline and widespread T-cell infiltration and organ damage. Mechanistic analysis showed activation and possible counter-regulation, with rapid T-cell expansion and accumulation of CD8(+) and CD4(+) granzyme B(+) effector cells and FoxP3(pos)/CD27(high)/CD25(pos)/CD127(low) CD4(+) T cells. CD8(+) cells down-regulated CD127 and BCl-2 and up-regulated Ki-67, consistent with a highly activated, proliferative profile. A cytokine storm also occurred, with GVHD-specific secretion of interleukin-1 receptor antagonist (IL-1Ra), IL-18, and CCL4. Costimulation Blockade and Sirolimus (CoBS) resulted in striking protection against GVHD. At the 30-day primary endpoint, CoBS-treated recipients showed 100% survival compared with no survival in untreated recipients. CoBS treatment resulted in survival, increasing from 11.6 to 62 days (P < .01) with blunting of T-cell expansion and activation. Some CoBS-treated animals did eventually develop GVHD, with both clinical and histopathologic evidence of smoldering disease. The reservoir of CoBS-resistant breakthrough immune activation included secretion of interferon-γ, IL-2, monocyte chemotactic protein-1, and IL-12/IL-23 and proliferation of cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-resistant CD28(-) CD8(+) T cells, suggesting adjuvant treatments targeting this subpopulation will be needed for full disease control.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.