ArticleTransplantation2010
Acute cardiac allograft rejection by directly cytotoxic CD4 T cells: parallel requirements for Fas and perforin.
Article in Transplantation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Cytomegalovirus Drives the Development of Cytotoxic CD4Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Single cell-resolved cellular, transcriptional, and epigenetic changes in mouse T cell populations linked to age-associated immune decline.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Expression of viral CD45 ligand E3/49K on porcine cells reduces human anti-pig immune responses.Scientific reports · 2023Article
- CD4Aging and disease · 2022Article
- Imaging strategies for monitoring the immune response.Chemical science · 2022Review
- Reduced Satb1 expression predisposes CD4Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- When Helpers Go Above and Beyond: Development and Characterization of Cytotoxic CD4Frontiers in immunology · 2022Review
- A strategy to protect off-the-shelf cell therapy products using virus-specific T-cells engineered to eliminate alloreactive T-cells.Journal of translational medicine · 2019Article
- Interferon Gamma and Contact-dependent Cytotoxicity Are Each Rate Limiting for Natural Killer Cell-Mediated Antibody-dependent Chronic Rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016Article
- Direct and indirect allograft recognition: pathways dictating graft rejection mechanisms.Current opinion in organ transplantation · 2016Review
- A CB2-Selective Cannabinoid Suppresses T-Cell Activities and Increases Tregs and IL-10.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
- Ectopic expression of Fas Ligand on cardiomyocytes renders cardiac allografts resistant to CD4(+) T-cell mediated rejection.Cellular immunology · 2015Article
- Murine heterotopic heart transplant technique.Journal of visualized experiments : JoVE · 2014Article
- Cytokine-dependent induction of CD4+ T cells with cytotoxic potential during influenza virus infection.Journal of virology · 2013Article
- Transient lymphopenia breaks costimulatory blockade-based peripheral tolerance and initiates cardiac allograft rejection.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2013Article
- Prolongation of cardiac allograft survival by a novel population of autologous CD117+ bone marrow-derived progenitor cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2011Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundCD4 T cells can suffice as effector cells to mediate primary acute cardiac allograft rejection. Although CD4 T cells can readily kill appropriate target cells in vitro, the corresponding role of such cytolytic activity for mediating allograft rejection in vivo is unknown. Therefore, we determined whether the cytolytic effector molecules perforin (PFP) and/or FasL (CD95L) were necessary for CD4 T cell-mediated rejection in vivo.
methodsWild-type C3H(H-2) or Fas (CD95)-deficient C3Hlpr (H-2) hearts were transplanted into immune-deficient C57B6rag (H-2) mice. Then, recipients were reconstituted with naïve purified CD4 T cells from wild-type, PFP-deficient, or FasL (gld)-deficient T-cell donors.
resultsIn vitro, alloreactive CD4 T cells were competent to lyse donor major histocompatibility complex class II+ target cells, largely by a Fas-dependent mechanism. In vivo, the individual disruption of donor Fas expression (lpr) or CD4 T-cell-derived PFP had no significant impact on acute rejection. However, FasL-deficient (gld) CD4 T cells demonstrated delayed allograft rejection. Importantly, the simultaneous removal of both donor Fas expression and CD4 T-cell PFP completely abrogated acute rejection, despite the persistence of CD4 T cells within the graft.
conclusionsResults demonstrate that the direct rejection of cardiac allografts by CD4 effector T cells requires the alternative contribution of graft Fas expression and T cell PFP expression. To our knowledge, this is the first demonstration that cytolytic activity by CD4 T cells can play an obligate role for primary acute allograft rejection in vivo.
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