ArticleTransplantation2012
Cytotoxic effector function of CD4-independent, CD8(+) T cells is mediated by TNF-α/TNFR.
Article in Transplantation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 18 citations in OpenAlex.
- Immune Dysregulation and Persistent Symptoms: Insights into T Cell Dynamics in Post-COVID among Athletes from the CoSmo-S Study.Journal of clinical immunology · 2026Article
- Promoting APC function of B cells via reprogramming the fatty acid metabolism enhances anticancer immunity in metastatic ovarian cancer.Cancer immunology, immunotherapy : CII · 2026Article
- The dual role of T cells in solid organ transplant rejection and immune tolerance.Frontiers in immunology · 2026Review
- Mechanistic insights into neutrophil involvement in liver transplant ischemia-reperfusion injury and rejection.Frontiers in immunology · 2026Review
- TFNR2 in Ischemia-Reperfusion Injury, Rejection, and Tolerance in Transplantation.Frontiers in immunology · 2022Review
- Invariant NKT Cells Promote the Development of Highly Cytotoxic Multipotent CXCR3Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Transcriptome and Function of Novel Immunosuppressive Autoreactive Invariant Natural Killer T Cells That Are Absent in Progressive Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2021Article
- Critical Role of Macrophage FcγR Signaling and Reactive Oxygen Species in Alloantibody-Mediated Hepatocyte Rejection.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Preferential TNFJCI insight · 2017Article
- Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- T Lymphocyte Subsets and Cytokines in Rats Transplanted with Adipose-Derived Mesenchymal Stem Cells and Acellular Nerve for Repairing the Nerve Defects.Journal of Korean Neurosurgical Society · 2015Article
- Alloprimed CD8(+) T cells regulate alloantibody and eliminate alloprimed B cells through perforin- and FasL-dependent mechanisms.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2014Article
- HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2013Article
- Soluble TNF-alpha-receptors I are prognostic markers in TIPS-treated patients with cirrhosis and portal hypertension.PloS one · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundLiver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8(+) T cell-mediated acute rejection pathways. The magnitude of allospecific CD8(+) T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4(+) T cells. The current studies were conducted to determine if and how CD4(+) T cells might influence cytotoxic effector mechanisms.
methodsMice were transplanted with allogeneic hepatocytes. In vivo cytotoxicity assays and various gene-deficient recipient mice and target cells were used to determine the development of Fas-, TNF-α-, and perforin-dependent cytotoxic effector mechanisms after transplantation.
resultsCD8(+) T cells maturing in CD4-sufficient hepatocyte recipients develop multiple (Fas-, TNF-α-, and perforin-mediated) cytotoxic mechanisms. However, CD8(+) T cells, maturing in the absence of CD4(+) T cells, mediate cytotoxicity and transplant rejection that is exclusively TNF-α/TNFR-dependent. To determine the kinetics of CD4-mediated help, CD4(+) T cells were adoptively transferred into CD4-deficient mice at various times posttransplant. The maximal influence of CD4(+) T cells on the magnitude of CD8-mediated in vivo allocytotoxicityf occurs within 48 hours.
conclusionThe implication of these studies is that interference of CD4(+) T cell function by disease or immunotherapy will have downstream consequences on both the magnitude of allocytotoxicity as well as the cytotoxic effector mechanisms used by allospecific CD8(+) cytolytic 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.