CD4 T cell

Where it participates (unsigned role)

1. A subset of GABA-A receptor subunits are expressed by CD4-positive T cells including the delta subunit that confers high affinity for GABA and sensitivity to alcohol, GABA at relatively low concentrations down-regulated effector T cell responses to beta cell antigens ex vivo and administration of GABA retarded the adoptive transfer of type 1 diabetes in NOD/scid mice, treatment with a low dose of GABA at 600 micrograms daily dramatically inhibited the development of proinflammatory T cell responses and disease progression in disease-prone mice that already had established autoimmunity, and GABA inhibited T cell receptor-mediated T cell cycle progression in vitro which may underlie the therapeutic effects.

   Gamma-aminobutyric acid → Type 1 diabetes source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/15470076.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09", "start_char": 0, "end_char": 1443, "text_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09"}

   experimental_model

   Subunit analysis with ex vivo antigen responses, adoptive transfer and treatment of disease-prone mice

   exposure

   GABA at low concentrations ex vivo, and 600 micrograms daily in mice with established autoimmunity

   limitations

   A mouse type 1 diabetes model. The cell cycle result offers a mechanism for the disease effect but is measured separately from it.

   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

   Low doses slowed the immune attack on the insulin-producing cells even after that attack had already started.

   primary_references

   [gb-p15470076] Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model. (2004). https://pubmed.ncbi.nlm.nih.gov/15470076/ DOI: 10.4049/jimmunol.173.8.5298

   tissue_or_cell_type

   CD4 T cell and pancreatic islet

   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 534–545

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Subunit analysis with ex vivo antigen responses, adoptive transfer and treatment of disease-prone mice · source_derived_draft · unverified_draft

   ### gb-gaba-slows-the-autoimmune-t-cell A subset of GABA-A receptor subunits are expressed by CD4-positive T cells including the delta subunit that confers high affinity for GABA and sensitivity to alcohol, GABA at relatively low concentrations down-regulated effector T cell responses to beta cell antigens ex vivo and administration of GABA retarded the adoptive transfer of type 1 diabetes in NOD/scid mice, treatment with a low dose of GABA at 600 micrograms daily dramatically inhibited the development of proinflammatory T cell responses and disease progression in disease-prone mice that already had established autoimmunity, and GABA inhibited T cell receptor-mediated T cell cycle progression in vitro which may underlie the therapeutic effects. 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: Low doses slowed the immune attack on the insulin-producing cells even after that attack had already started. organism: Mouse tissue_or_cell_type: CD4 T cell and pancreatic islet experimental_model: Subunit analysis with ex vivo antigen responses, adoptive transfer and treatment of disease-prone mice limitations: A mouse type 1 diabetes model. The cell cycle result offers a mechanism for the disease effect but is measured separately from it. exposure: GABA at low concentrations ex vivo, and 600 micrograms daily in mice with established autoimmunity evidence_span: {"source_cache": "artifacts/gaba-research/15470076.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09", "start_char": 0, "end_char": 1443, "text_sha256": "e5523c02fc4571d5ab6c23776794b4b5cf025fb86cdba9acdc12011f3a6b2e09"} [gb-p15470076] Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model. (2004). https://pubmed.ncbi.nlm.nih.gov/15470076/ DOI: 10.4049/jimmunol.173.8.5298

   Complete structured claim and evidence

2. There were 5, 8 and 13 different GABA-A subunit isoforms identified in human, mouse and rat CD4-positive and CD8-positive T cells respectively, importantly the gamma2 subunit that imposes benzodiazepine sensitivity on the GABA-A receptors was only detected in the mouse T cells, immunoblots and immunocytochemistry showed abundant GABA-A channel proteins in T cells from all three species, GABA-activated whole-cell transient and tonic currents were recorded and were inhibited by picrotoxin, SR95531 and bicuculline, and it is important to bear in mind the interspecies difference when selecting the appropriate animal models and when selecting drugs aimed at modulating human T cell function.

   The GABA-A receptor subunit repertoire of a cell → GABA-A receptor anion channels source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/gaba-research/22927941.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0457001832d2a3595899415221b7797f5288a787c1d52fd6afa1acf24f032402", "start_char": 0, "end_char": 1589, "text_sha256": "0457001832d2a3595899415221b7797f5288a787c1d52fd6afa1acf24f032402"}

   experimental_model

   Subunit isoform survey with immunoblotting, immunocytochemistry and whole-cell recording across three species

   exposure

   GABA-activated transient and tonic currents, with picrotoxin, SR95531 and bicuculline

   limitations

   The species comparison is the point. Subunit repertoires differ enough that a drug result in one species does not carry to another.

   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

   Human, mouse and rat

   plain_language

   The subunit that makes a receptor respond to benzodiazepines was found on mouse T cells and not on human ones.

   primary_references

   [gb-p22927941] Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes. (2012). https://pubmed.ncbi.nlm.nih.gov/22927941/ DOI: 10.1371/journal.pone.0042959

   tissue_or_cell_type

   CD4 and CD8 T lymphocytes

   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 521–532

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Subunit isoform survey with immunoblotting, immunocytochemistry and whole-cell recording across three species · source_derived_draft · unverified_draft

   ### gb-the-subunits-differ-by-species There were 5, 8 and 13 different GABA-A subunit isoforms identified in human, mouse and rat CD4-positive and CD8-positive T cells respectively, importantly the gamma2 subunit that imposes benzodiazepine sensitivity on the GABA-A receptors was only detected in the mouse T cells, immunoblots and immunocytochemistry showed abundant GABA-A channel proteins in T cells from all three species, GABA-activated whole-cell transient and tonic currents were recorded and were inhibited by picrotoxin, SR95531 and bicuculline, and it is important to bear in mind the interspecies difference when selecting the appropriate animal models and when selecting drugs aimed at modulating human T cell function. 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 subunit that makes a receptor respond to benzodiazepines was found on mouse T cells and not on human ones. organism: Human, mouse and rat tissue_or_cell_type: CD4 and CD8 T lymphocytes experimental_model: Subunit isoform survey with immunoblotting, immunocytochemistry and whole-cell recording across three species limitations: The species comparison is the point. Subunit repertoires differ enough that a drug result in one species does not carry to another. exposure: GABA-activated transient and tonic currents, with picrotoxin, SR95531 and bicuculline evidence_span: {"source_cache": "artifacts/gaba-research/22927941.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0457001832d2a3595899415221b7797f5288a787c1d52fd6afa1acf24f032402", "start_char": 0, "end_char": 1589, "text_sha256": "0457001832d2a3595899415221b7797f5288a787c1d52fd6afa1acf24f032402"} [gb-p22927941] Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes. (2012). https://pubmed.ncbi.nlm.nih.gov/22927941/ DOI: 10.1371/journal.pone.0042959

   Complete structured claim and evidence

3. Rara-deficient or RAR-antagonized T cells proliferated less efficiently after stimulation.

   Retinoic acid receptor alpha → CD4 T-cell proliferation source_derived_draftungraded
   Experimental context and source evidence

   availability_state

   machinery_impairment Imported condition classification; unverified.

   evidence_locator

   Discussion and T-cell activation experiments

   experimental_model

   Vitamin A-insufficient and Rara-deficient mice; stimulated CD4 T cells.

   exposure

   Rara loss or RAR antagonism

   limitations

   Does not negate RA effects on Treg differentiation.

   nutrient_topic

   Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

   organism

   Mus musculus

   plain_language

   Loss of receptor signaling can weaken effector-cell expansion.

   primary_references

   [va-hall-2011] Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3415227/ DOI: 10.1016/j.immuni.2011.03.003

   tissue_or_cell_type

   CD4 T cells

   trigger_kind

   machinery_impairment Imported condition classification; unverified.

   Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1279–1290

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Vitamin A-insufficient and Rara-deficient mice; stimulated CD4 T cells. · source_derived_draft · unverified_draft

   ### va-sig-rara-t-cell-proliferation Rara-deficient or RAR-antagonized T cells proliferated less efficiently after stimulation. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of receptor signaling can weaken effector-cell expansion. organism: Mus musculus tissue_or_cell_type: CD4 T cells experimental_model: Vitamin A-insufficient and Rara-deficient mice; stimulated CD4 T cells. limitations: Does not negate RA effects on Treg differentiation. evidence_locator: Discussion and T-cell activation experiments exposure: Rara loss or RAR antagonism [va-hall-2011] Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3415227/ DOI: 10.1016/j.immuni.2011.03.003

   Complete structured claim and evidence