ArticleJournal of immunology (Baltimore, Md. : 1950)2008
A critical precursor frequency of donor-reactive CD4+ T cell help is required for CD8+ T cell-mediated CD28/CD154-independent rejection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
21 citing papers in PubMed, 31 citations in OpenAlex.
- Renal transplantation using belatacept without maintenance steroids or calcineurin inhibitors.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Trial
- Best practices in mouse models of skin transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Review
- Article
- Co-inhibitory Receptor Signaling in T-Cell-Mediated Autoimmune Glomerulonephritis.Frontiers in medicine · 2020Review
- Challenges and opportunities in targeting the CD28/CTLA-4 pathway in transplantation and autoimmunity.Expert opinion on biological therapy · 2017Review
- Update on CD40 and CD154 blockade in transplant models.Immunotherapy · 2015Review
- 2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses.The Journal of experimental medicine · 2014Article
- Targeting co-stimulatory pathways: transplantation and autoimmunity.Nature reviews. Nephrology · 2014Review
- Article
- CTLA4Ig prevents alloantibody formation following nonhuman primate islet transplantation using the CD40-specific antibody 3A8.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2012Article
- CD28 family and chronic rejection: "to belatacept...And beyond!".Journal of transplantation · 2012Article
- Antigen-specific induced Foxp3+ regulatory T cells are generated following CD40/CD154 blockade.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- CD28 blockade induces division-dependent downregulation of interleukin-2 receptor alpha.Transplant immunology · 2011Article
- Selective targeting of human alloresponsive CD8+ effector memory T cells based on CD2 expression.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011Article
- B cells and transplantation tolerance.Nature reviews. Nephrology · 2010Review
- Overcoming the memory barrier in tolerance induction: molecular mimicry and functional heterogeneity among pathogen-specific T-cell populations.Current opinion in organ transplantation · 2010Review
- High-frequency alloreactive T cells augment effector function of low-frequency CD8+ T-cell responses under CD28/CD154 blockade.Transplantation · 2010Article
- Anti-CD40 monoclonal antibody synergizes with CTLA4-Ig in promoting long-term graft survival in murine models of transplantation.Journal of immunology (Baltimore, Md. : 1950) · 2009Article
- Donor-reactive T-cell stimulation history and precursor frequency: barriers to tolerance induction.Transplantation · 2009Review
- Translating costimulation blockade to the clinic: lessons learned from three pathways.Immunological reviews · 2009Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Ag-specific precursor frequency is increasingly being appreciated as an important factor in determining the kinetics, magnitude, and degree of differentiation of T cell responses, and recently was found to play a critical role in determining the relative requirement of CD8(+) T cells for CD28- and CD154-mediated costimulatory signals during transplantation. We addressed the possibility that variations in CD4(+) T cell precursor frequency following transplantation might affect CD4(+) T cell proliferation, effector function, and provision of help for donor-reactive B cell and CD8(+) T cell responses. Using a transgenic model system wherein increasing frequencies of donor-reactive CD4(+) T cells were transferred into skin graft recipients, we observed that a critical CD4(+) T cell threshold precursor frequency was necessary to provide help following blockade of the CD28 and CD154 costimulatory pathways, as measured by increased B cell and CD8(+) T cell responses and precipitation of graft rejection. In contrast to high-frequency CD8(+) T cell responses, this effect was observed even though the proliferative and cytokine responses of Ag-specific CD4(+) T cells were inhibited. Thus, we conclude that an initial high frequency of donor-reactive CD4(+) T cells uncouples T cell proliferative and effector cytokine production from the provision of T cell help.
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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.