ArticleImmunology2009
Switch from perforin-expressing to perforin-deficient CD8(+) T cells accounts for two distinct types of effector cytotoxic T lymphocytes in vivo.
Article in Immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
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- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- The application of antibody-based agents in cancer therapy based on their mechanisms of action.Fundamental research · 2025Review
- B2M or CIITA knockdown decreased the alloimmune response of dental pulp stem cells: an in vitro study.Stem cell research & therapy · 2024Article
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- Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.Cell death & disease · 2024Article
- Host immune responses against African swine fever virus: Insights and challenges for vaccine development.Open veterinary journal · 2023Review
- Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4.International journal of molecular sciences · 2023Article
- Who wins the combat, CAR or TCR?Leukemia · 2023Review
- Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours.Nature reviews. Clinical oncology · 2023Review
- Modern Advances in CARs Therapy and Creating a New Approach to Future Treatment.International journal of molecular sciences · 2022Review
- Anti-Apoptotic c-FLIP Reduces the Anti-Tumour Activity of Chimeric Antigen Receptor T Cells.Cancers · 2022Article
- Adaptive Cellular Immunity against African Swine Fever Virus Infections.Pathogens (Basel, Switzerland) · 2022Review
- Chimeric antigen receptor engineered T cells and their application in the immunotherapy of solid tumours.Expert reviews in molecular medicine · 2022Review
- Advances in CAR T-cell therapy in bile duct, pancreatic, and gastric cancers.Frontiers in immunology · 2022Review
- Cytotoxic Efficiency of Human CD8Frontiers in immunology · 2022Article
- The long road to TRAIL therapy: a TRAILshort detour.Oncotarget · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although CD8(+) cytotoxic T lymphocytes (CTL) exhibit both Fas ligand (FasL) -based and perforin-based lytic activities, the accepted hallmark of a fully active CTL remains its perforin killing machinery. Yet the origin, rationale for possessing both a slow-acting (FasL) and a fast-acting (perforin) killing mechanism has remained enigmatic. Here we have investigated perforin expression in CTL directly involved in acute tumour (i.e. leukaemias EL4 and L1210) allograft rejection occurring within the peritoneal cavity. We show that at the height of the immune response, the majority of conjugate-forming CD8(+) CTL express high levels of perforin messenger RNA and protein, and kill essentially via perforin. Later however, coinciding with complete rejection, fully cytocidal CTL emerge which exhibit a stark decrease in perforin and now kill preferentially via constitutively expressed FasL. Although late in emergence, and persistent, these powerful CTL are neither effector-memory nor memory CTL. This finding has implications for the monitoring of anti-transplant responses in clinical settings, based on assessing perforin expression in graft infiltrating CD8(+) T cells. The results show that as the immune response progresses in vivo, targeted cellular suicide mainly prunes high perforin-expressing CD8(+) cells, resulting in the gradual switch in effector CTL, from mostly perforin-based to largely Fas/FasL-based killers. Hence, two kinds of CD8(+) CTL have two killing strategies.
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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.