ArticleBMC immunology2014
Granzyme B secretion by human memory CD4 T cells is less strictly regulated compared to memory CD8 T cells.
Article in BMC immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 87 citations in OpenAlex.
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- Antibody-targeted T cells and natural killer cells for cancer immunotherapy.Journal of nanobiotechnology · 2024Article
- Granzyme B-activated IL18 potentiates αβ and γδ CAR T cell immunotherapy in a tumor-dependent manner.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- STING-activating cyclic dinucleotide-manganese nanoparticles evoke robust immunity against acute myeloid leukemia.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Does the expression of granzyme B participate in inflammation, fibrosis, and fertility of hydatid cysts?Parasitology research · 2023Article
- Complementary HLH susceptibility factors converge on CD8 T-cell hyperactivation.Blood advances · 2023Article
- HIF-1 regulates pathogenic cytotoxic T cells in lupus skin disease.JCI insight · 2023Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundGranzyme B (GrzB) is a serine proteinase expressed by memory T cells and NK cells. Methods to measure GrzB protein usually involve intracellular (flow cytometry) and extracellular (ELISA and ELISpot) assays. CD8 T cells are the main source of GrzB during immunological reactions, but activated CD4 T cells deploy GrzB as well. Because GrzB is an important mediator of cell death, tissue pathology and disease, clarification of differences of GrzB expression and secretion between CD4 and CD8 T cells is important for understanding effector functions of these cells.
resultsMemory CD4 and memory CD8 T cells were purified from human peripheral blood of healthy donors, and production of GrzB was directly compared between memory CD4 and memory CD8 T cells from the same donors using parallel measurements of flow cytometry (intracellular GrzB), ELISpot (single cell secretion of GrzB), and ELISA (bulk extracellular GrzB). Memory CD8 T cells constitutively stored significantly more GrzB protein (~25%) compared to memory CD4 T cells as determined by flow cytometry (~3%), and this difference remained stable after 24 hrs of activation. However, measurement of extracellular GrzB by ELISA revealed that activated memory CD4 T cells secrete similar amounts of GrzB (~1,000 pg/ml by 1x10(5) cells/200 μl medium) compared to memory CD8 T cells (~600 pg/ml). Measurement of individual GrzB-secreting cells by ELISpot also indicated that similar numbers of activated memory CD4 (~170/1x10(5)) and memory CD8 (~200/1x10(5)) T cells secreted GrzB. Expression of CD107a further indicated that Grzb is secreted similarly by activated CD4 and CD8 T cells, consistent with the ELISA and ELISpot results. However, memory CD8 T cells expressed and secreted more perforin compared to memory CD4 T cells, suggesting that perforin may be less associated with GrzB function for memory CD4 T cells.
conclusionsAlthough measurement of intracellular GrzB by flow cytometry suggests that a larger proportion of CD8 T cells have higher capacity for GrzB production compared to CD4 T cells, ELISpot and ELISA show that similar numbers of activated CD4 and CD8 T cells secrete similar amounts of GrzB. Secretion of GrzB by activated CD8 T cells may be more tightly controlled compared to CD4 T cells.
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