CD8 T cell killer function

Where it participates (unsigned role)

1. We identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells, B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8-positive T cell killer function, and in mice B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses.

   B cell → Gamma-aminobutyric acid source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/34732892.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b", "start_char": 0, "end_char": 878, "text_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b"}

   experimental_model

   Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice

   exposure

   B cell-derived GABA, with B cell deficiency and B cell-specific inactivation of the GABA-generating enzyme GAD67

   limitations

   The B cell-specific enzyme deletion is what makes the source assignment strong. The enzyme deleted is GAD67, not the GAD65 that is the diabetes autoantigen.

   nutrient_topic

   GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

   organism

   Mouse

   plain_language

   B cells release this molecule into a tumour, where it turns arriving monocytes into cells that shut down the killers.

   primary_references

   [gb-p34732892] B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. (2021). https://pubmed.ncbi.nlm.nih.gov/34732892/ DOI: 10.1038/s41586-021-04082-1

   tissue_or_cell_type

   B cell, monocyte and tumour

   GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 599–610

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice · source_derived_draft · unverified_draft

   ### gb-b-cells-secrete-gaba-that-shields-tumours We identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells, B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8-positive T cell killer function, and in mice B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: B cells release this molecule into a tumour, where it turns arriving monocytes into cells that shut down the killers. organism: Mouse tissue_or_cell_type: B cell, monocyte and tumour experimental_model: Identification of a metabolite secreted by activated B cells, with monocyte differentiation and two genetic tests in mice limitations: The B cell-specific enzyme deletion is what makes the source assignment strong. The enzyme deleted is GAD67, not the GAD65 that is the diabetes autoantigen. exposure: B cell-derived GABA, with B cell deficiency and B cell-specific inactivation of the GABA-generating enzyme GAD67 evidence_span: {"source_cache": "artifacts/gaba-research/34732892.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b", "start_char": 0, "end_char": 878, "text_sha256": "907d2a95afcac30a55ebfa4a6056c31ca53c452caff350ded70a60c9fc2eb17b"} [gb-p34732892] B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity. (2021). https://pubmed.ncbi.nlm.nih.gov/34732892/ DOI: 10.1038/s41586-021-04082-1

   Complete structured claim and evidence

2. Necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours causing profound suppression of T cell effector function, elevation of the extracellular potassium concentration impairs T cell receptor-driven Akt-mTOR phosphorylation and effector programmes, potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A, although the suppressive effect mediated by elevated extracellular potassium is independent of changes in plasma membrane potential it requires an increase in intracellular potassium, and augmenting potassium efflux in tumour-specific T cells by overexpressing the potassium channel Kv1.3 lowers intracellular potassium and improves effector functions in vitro and in vivo.

   Intracellular potassium concentration → TCR-driven Akt-mTOR phosphorylation source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/27626381.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73f83e208d8ad23be6c7ada4127b06536cdfd3156c4ac588e004e775761214f8", "start_char": 0, "end_char": 1240, "text_sha256": "73f83e208d8ad23be6c7ada4127b06536cdfd3156c4ac588e004e775761214f8"}

   experimental_model

   Measurement of potassium released by tumour necrosis with T cell signalling, phosphatase dependency and channel overexpression in melanoma-bearing mice

   exposure

   Elevated extracellular potassium from necrotic tumour areas, with Kv1.3 overexpression in tumour-specific T cells

   limitations

   Included here because it is routinely placed alongside the tumour GABA story. Its own abstract states that the suppression is independent of changes in plasma membrane potential, which is the opposite of what that pairing usually assumes.

   nutrient_topic

   GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. · Gamma-aminobutyric acid

   organism

   Mouse and human

   plain_language

   The tumour potassium that disarms T cells does so by getting inside them and switching on a phosphatase, not by changing the voltage across the membrane.

   primary_references

   [gb-p27626381] Ionic immune suppression within the tumour microenvironment limits T cell effector function. (2016). https://pubmed.ncbi.nlm.nih.gov/27626381/ DOI: 10.1038/nature19364

   tissue_or_cell_type

   Tumour microenvironment and T cell

   GABA: a ligand with no sign of its own, the cofactor that limits its synthesis, the barrier that keeps it out of the brain, and the immune settings where the same molecule protects and harms (2026-09-22) · lines 612–623

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Measurement of potassium released by tumour necrosis with T cell signalling, phosphatase dependency and channel overexpression in melanoma-bearing mice · source_derived_draft · unverified_draft

   ### gb-the-potassium-effect-is-not-electrical Necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours causing profound suppression of T cell effector function, elevation of the extracellular potassium concentration impairs T cell receptor-driven Akt-mTOR phosphorylation and effector programmes, potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A, although the suppressive effect mediated by elevated extracellular potassium is independent of changes in plasma membrane potential it requires an increase in intracellular potassium, and augmenting potassium efflux in tumour-specific T cells by overexpressing the potassium channel Kv1.3 lowers intracellular potassium and improves effector functions in vitro and in vivo. Condition category: normal nutrient_topic: GABA research collection; topical membership is not evidence of a direct clinical effect, and the sign of a GABA response depends on the chloride gradient of the cell it was measured in. plain_language: The tumour potassium that disarms T cells does so by getting inside them and switching on a phosphatase, not by changing the voltage across the membrane. organism: Mouse and human tissue_or_cell_type: Tumour microenvironment and T cell experimental_model: Measurement of potassium released by tumour necrosis with T cell signalling, phosphatase dependency and channel overexpression in melanoma-bearing mice limitations: Included here because it is routinely placed alongside the tumour GABA story. Its own abstract states that the suppression is independent of changes in plasma membrane potential, which is the opposite of what that pairing usually assumes. exposure: Elevated extracellular potassium from necrotic tumour areas, with Kv1.3 overexpression in tumour-specific T cells evidence_span: {"source_cache": "artifacts/gaba-research/27626381.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73f83e208d8ad23be6c7ada4127b06536cdfd3156c4ac588e004e775761214f8", "start_char": 0, "end_char": 1240, "text_sha256": "73f83e208d8ad23be6c7ada4127b06536cdfd3156c4ac588e004e775761214f8"} [gb-p27626381] Ionic immune suppression within the tumour microenvironment limits T cell effector function. (2016). https://pubmed.ncbi.nlm.nih.gov/27626381/ DOI: 10.1038/nature19364

   Complete structured claim and evidence