Page last updated: 2024-10-24

CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation

Definition

Target type: biologicalprocess

The process in which a precursor cell type acquires the specialized features of a CD4-positive, CD25-positive, alpha-beta regulatory T cell. [GOC:add, PMID:15207821]

CD4-positive, CD25-positive, alpha-beta regulatory T cells (Tregs) are a specialized subset of T lymphocytes that play a critical role in maintaining immune homeostasis and preventing autoimmunity. Their differentiation is a complex process involving multiple signaling pathways and transcription factors. Here's a detailed breakdown:

1. **Development in the Thymus:** Tregs originate in the thymus, where they undergo a unique developmental program. During thymic development, immature T cells encounter self-antigens presented by thymic epithelial cells. This interaction can lead to two distinct outcomes:
* **Positive selection:** T cells recognizing self-antigens with low affinity undergo positive selection, ensuring that they can recognize self-MHC molecules but not attack self-tissues.
* **Negative selection:** T cells recognizing self-antigens with high affinity undergo negative selection, eliminating cells that could potentially cause autoimmunity.

2. **Treg Specification:** A subset of thymocytes that undergo positive selection encounter self-antigens presented by thymic epithelial cells in the context of a specific co-stimulatory molecule, CTLA4. This interaction, along with the cytokine TGF-β, triggers the expression of the transcription factor Foxp3. Foxp3 is the master regulator of Treg development and function, and its expression marks the commitment of these cells to the Treg lineage.

3. **Peripheral Induction:** While the majority of Tregs develop in the thymus, a significant portion can be generated in the periphery from naive CD4+ T cells, a process known as peripheral Treg induction. This induction requires specific conditions, including:
* **Exposure to self-antigens:** Naive CD4+ T cells encounter self-antigens in the periphery.
* **Presence of TGF-β:** TGF-β acts as a crucial cytokine for Treg induction, triggering Foxp3 expression and promoting the differentiation of naive CD4+ T cells into induced Tregs.
* **Other factors:** Additional factors, like retinoic acid, IL-2, and IL-10, can also influence peripheral Treg induction.

4. **Treg Function:** Mature Tregs exhibit several key characteristics:
* **Suppression of Immune Responses:** Tregs suppress the activation and proliferation of other immune cells, such as conventional T cells, preventing excessive immune responses and autoimmunity.
* **Immunosuppressive Mechanisms:** Tregs use various mechanisms to suppress immune responses:
* **Cytokine Production:** They produce immunosuppressive cytokines like IL-10 and TGF-β, which dampen the activity of other immune cells.
* **Depletion of T cell co-stimulatory molecules:** Tregs express CTLA4, a molecule that competes with CD28 for binding to CD80/CD86 on antigen-presenting cells (APCs), reducing T cell activation.
* **Metabolic Modulation:** Tregs can deplete the local environment of nutrients like glucose, hindering the metabolic requirements of other T cells.
* **Direct cell-cell contact:** Tregs can directly interact with other immune cells, inducing their apoptosis or suppressing their function.

5. **Treg Stability and Plasticity:** Tregs are generally considered stable, maintaining their suppressive function over time. However, they can exhibit some degree of plasticity, under certain conditions, differentiating into other T cell subsets like Th17 cells.

6. **Importance in Immune Homeostasis:** Tregs play a critical role in maintaining immune tolerance by preventing excessive immune responses against self-antigens and controlling immune responses against commensal bacteria and other environmental antigens. Dysregulation of Treg function can lead to autoimmune diseases and other immune-related disorders.'
"

Proteins (2)

ProteinDefinitionTaxonomy
Group IID secretory phospholipase A2A group IID secretory phospholipase A2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UNK4]Homo sapiens (human)
Alpha-(1,3)-fucosyltransferase 7An alpha-(1,3)-fucosyltransferase 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q11130]Homo sapiens (human)

Compounds (14)

CompoundDefinitionClassesRoles
2,3-dihydroxybenzoic acid2,3-dihydroxybenzoic acid : A dihydroxybenzoic acid that is benzoic acid substituted by hydroxy groups at positions 2 and 3. It occurs naturally in Phyllanthus acidus and in the aquatic fern Salvinia molesta.

2,3-dihydroxybenzoic acid: RN given refers to parent cpd

dihydroxybenzoic acid : Any member of the class of hydroxybenzoic acids carrying two phenolic hydroxy groups on the benzene ring and its derivatives.
dihydroxybenzoic acidhuman xenobiotic metabolite;
plant metabolite
protocatechuic acid3,4-dihydroxybenzoic acid : A dihydroxybenzoic acid in which the hydroxy groups are located at positions 3 and 4.

protocatechuic acid: RN given refers to parent cpd; structure
catechols;
dihydroxybenzoic acid
antineoplastic agent;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor;
human xenobiotic metabolite;
plant metabolite
gallic acidgallate : A trihydroxybenzoate that is the conjugate base of gallic acid.trihydroxybenzoic acidantineoplastic agent;
antioxidant;
apoptosis inducer;
astringent;
cyclooxygenase 2 inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
geroprotector;
human xenobiotic metabolite;
plant metabolite
beta-resorcylic acidbeta-resorcylic acid: RN given refers to parent cpd; structure
2,5-dihydroxybenzoic acid2,5-dihydroxybenzoic acid : A dihydroxybenzoic acid having the two hydroxy groups at the 2- and 5-positions.

2,5-dihydroxybenzoic acid: RN given refers to parent cpd; a oxidative product of saligenin
dihydroxybenzoic acidEC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
fungal metabolite;
human metabolite;
MALDI matrix material;
mouse metabolite
veratric acid3,4-dimethoxybenzoic acid : A member of the class of benzoic acids that is benzoic acid substituted by methoxy groups at positions 2 and 3.

veratric acid: RN given refers to parent cpd; structure
benzoic acidsallergen;
plant metabolite
methyl gallatemethyl 3,4,5-trihydroxybenzoate : A gallate ester obtained by the formal condensation of gallic acid with methanol. It exhibits anti-oxidant, anti-tumor, anti-microbial and anti-inflammatory properties.

methyl gallate: has both immunosuppressive and phytogenic antineoplastic activities; isolated from Acer saccharinum
gallate esteranti-inflammatory agent;
antioxidant;
plant metabolite
3,4,5-trimethoxybenzoic acid3,4,5-trimethoxybenzoic acid : A benzoic acid derivative carrying 3-, 4- and 5-methoxy substituents.

3,4,5-trimethoxybenzoic acid: RN given refers to parent cpd; structure
benzoic acids;
methoxybenzenes
human urinary metabolite;
human xenobiotic metabolite;
plant metabolite
syringic acidsyringic acid : A dimethoxybenzene that is 3,5-dimethyl ether derivative of gallic acid.

syringic acid: RN given refers to parent cpd; structure in third source
benzoic acids;
dimethoxybenzene;
phenols
plant metabolite
epigallocatechin gallate(-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin.

epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis)
flavans;
gallate ester;
polyphenol
antineoplastic agent;
antioxidant;
apoptosis inducer;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent;
plant metabolite
3-octylthio-1,1,1-trifluoro-2-propanone3-octylthio-1,1,1-trifluoro-2-propanone: a pesticide synergist; inhibits juvenile hormone esterase
varespladibaromatic ether;
benzenes;
dicarboxylic acid monoamide;
indoles;
monocarboxylic acid;
primary carboxamide
anti-inflammatory drug;
antidote;
EC 3.1.1.4 (phospholipase A2) inhibitor
indoxamindoxam: structure in first source
guanosine diphosphateGuanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.guanosine 5'-phosphate;
purine ribonucleoside 5'-diphosphate
Escherichia coli metabolite;
mouse metabolite;
uncoupling protein inhibitor