ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2013
CD40-independent help by memory CD4 T cells induces pathogenic alloantibody but does not lead to long-lasting humoral immunity.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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
26 citing papers in PubMed, 36 citations in OpenAlex.
- Best practices of heart transplantation in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Desensitization in HLA-incompatible kidney transplant recipients: current strategies and emerging perspectives.Clinical kidney journal · 2025Review
- [Immunological Aspects after Lung Transplantation].Zentralblatt fur Chirurgie · 2025Review
- Marginal zone B cells are required for optimal humoral responses to allograft.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- A candidate nanoparticle vaccine comprised of multiple epitopes of the African swine fever virus elicits a robust immune response.Journal of nanobiotechnology · 2023Article
- Water channel aquaporin 4 is required for T cell receptor mediated lymphocyte activation.Journal of leukocyte biology · 2023Article
- Memory B cells and long-lived plasma cells in AMR.Renal failure · 2022Review
- Macrophage-inducible C-type lectin activates B cells to promote T cell reconstitution in heart allograft recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022Article
- Superior inhibition of alloantibody responses with selective CD28 blockade is CTLA-4 dependent and T follicular helper cell specific.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- B cell-derived IL-1β and IL-6 drive T cell reconstitution following lymphoablation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Mechanisms of organ transplant injury mediated by B cells and antibodies: Implications for antibody-mediated rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Review
- Pre-existing Alloreactive T and B Cells and Their Possible Relevance for Pre-transplant Risk Estimation in Kidney Transplant Recipients.Frontiers in medicine · 2020Review
- Anti-donor MHC Class II Alloantibody Induces Glomerular Injury in Mouse Renal Allografts Subjected to Prolonged Cold Ischemia.Journal of the American Society of Nephrology : JASN · 2019Article
- Interleukin-27 promotes CD8+ T cell reconstitution following antibody-mediated lymphoablation.JCI insight · 2019Article
- Measuring alloreactive B cell responses in transplant recipients.Current transplantation reports · 2019Article
- Memory CD4 T Cells Induce Antibody-Mediated Rejection of Renal Allografts.Journal of the American Society of Nephrology : JASN · 2016Article
- T Cell Cosignaling Molecules in Transplantation.Immunity · 2016Review
- CD4 T Cell Help via B Cells Is Required for Lymphopenia-Induced CD8 T Cell Proliferation.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Mechanisms of antibody-mediated acute and chronic rejection of kidney allografts.Current opinion in organ transplantation · 2016Review
- T follicular helper cells in the generation of alloantibody and graft rejection.Current opinion in organ transplantation · 2016Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
CD40/CD154 interactions are essential for productive antibody responses to T-dependent antigens. Memory CD4 T cells express accelerated helper functions and are less dependent on costimulation when compared with naïve T cells. Here, we report that donor-reactive memory CD4 T cells can deliver help to CD40-deficient B cells and induce high titers of IgG alloantibodies that contribute to heart allograft rejection in CD40-/- heart recipients. While cognate interactions between memory helper T and B cells are crucial for CD40-independent help, this process is not accompanied by germinal center formation and occurs despite inducible costimulatory blockade. Consistent with the extrafollicular nature of T/B cell interactions, CD40-independent help fails to maintain stable levels of serum alloantibody and induce differentiation of long-lived plasma cells and memory B cells. In summary, our data suggest that while CD40-independent help by memory CD4 T cells is sufficient to induce high levels of pathogenic alloantibody, it does not sustain long-lasting anti-donor humoral immunity and B cell memory responses. This information may guide the future use of CD40/CD154 targeting therapies in transplant recipients containing donor-reactive memory T cells.
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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.