Page last updated: 2024-10-24

regulation of T cell proliferation

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of T cell proliferation. [GOC:jl]

The regulation of T cell proliferation is a complex process involving a intricate interplay of signaling pathways, transcription factors, and cytokines. T cell activation, the initial trigger for proliferation, begins with the engagement of the T cell receptor (TCR) with a specific antigen presented by an antigen-presenting cell (APC). This binding event initiates a cascade of intracellular signaling events, culminating in the activation of transcription factors like NF-κB and AP-1, which drive the expression of genes crucial for T cell proliferation, including those encoding growth factors and cell cycle regulators.

Among the key signaling pathways activated by TCR engagement is the MAPK pathway, which involves the sequential activation of kinases such as Ras, Raf, MEK, and ERK. ERK phosphorylation triggers the activation of several transcription factors, including AP-1, which in turn promotes the expression of genes involved in cell cycle progression and proliferation. Another crucial signaling pathway activated upon TCR stimulation is the PI3K-Akt pathway. PI3K, a lipid kinase, is activated by TCR-mediated signaling, leading to the phosphorylation of PIP2 into PIP3. PIP3 then activates the kinase Akt, which plays a pivotal role in regulating cell survival, growth, and metabolism, all of which are essential for T cell proliferation.

The activation of these signaling pathways results in the expression of various growth factors and cytokines that contribute to the expansion of T cells. Interleukin-2 (IL-2), a key cytokine produced by activated T cells, acts as a potent autocrine growth factor, stimulating the proliferation of T cells that express the IL-2 receptor. Furthermore, CD28, a co-stimulatory molecule expressed on T cells, enhances TCR signaling and promotes IL-2 production, further amplifying T cell proliferation.

Beyond signaling pathways and cytokine signaling, the regulation of T cell proliferation also involves the control of the cell cycle. Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression. The activity of CDKs is tightly regulated by cyclins, which are proteins that fluctuate in abundance throughout the cell cycle. Activation of CDKs by cyclins triggers the progression of the cell cycle through different phases, ultimately leading to cell division. The regulation of CDK activity is critical for ensuring that cells divide only when appropriate and that errors in DNA replication are minimized.

In addition to these positive regulators, there are also several negative regulators that fine-tune T cell proliferation. CTLA-4, a negative co-stimulatory molecule expressed on T cells, inhibits TCR signaling and IL-2 production, thus suppressing T cell proliferation. Similarly, PD-1, another inhibitory receptor, dampens TCR signaling and promotes T cell exhaustion, a state of functional impairment that limits T cell proliferation and effector function. These inhibitory mechanisms are important for preventing excessive T cell activation and autoimmune responses.

The precise mechanisms by which T cell proliferation is regulated can vary depending on the specific T cell subset and the context of the immune response. However, the overall process involves a complex interplay of signaling pathways, transcription factors, cytokines, and cell cycle regulators, ensuring that T cells expand appropriately in response to pathogens while maintaining immune homeostasis and preventing autoimmunity.'
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Proteins (5)

ProteinDefinitionTaxonomy
CD209 antigenA CD209 molecule that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q9NNX6]Homo sapiens (human)
BH3-interacting domain death agonistA BH3-interacting domain death agonist that is encoded in the genome of human. [PRO:WCB, UniProtKB:P55957]Homo sapiens (human)
B-cell lymphoma 6 proteinA B-cell lymphoma 6 protein that is encoded in the genome of human. [PRO:CNA, UniProtKB:P41182]Homo sapiens (human)
Catenin beta-1A catenin beta-1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P35222]Homo sapiens (human)
Galectin-3A galectin-3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P17931]Homo sapiens (human)

Compounds (28)

CompoundDefinitionClassesRoles
gossypolGossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer.
lactosebeta-lactose : The beta-anomer of lactose.

lactose : A glycosylglucose disaccharide, found most notably in milk, that consists of D-galactose and D-glucose fragments bonded through a beta-1->4 glycosidic linkage. The glucose fragment can be in either the alpha- or beta-pyranose form, whereas the galactose fragment can only have the beta-pyranose form.

Lactose: A disaccharide of GLUCOSE and GALACTOSE in human and cow milk. It is used in pharmacy for tablets, in medicine as a nutrient, and in industry.
lactose
amanozinediamino-1,3,5-triazine
fucosefucose : Any deoxygalactose that is deoxygenated at the 6-position.

Fucose: A six-member ring deoxysugar with the chemical formula C6H12O5. It lacks a hydroxyl group on the carbon at position 6 of the molecule.

L-fucopyranose : The pyranose form of L-fucose.
fucopyranose;
L-fucose
Escherichia coli metabolite;
mouse metabolite
mannosemannopyranose : The pyranose form of mannose.D-aldohexose;
D-mannose;
mannopyranose
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
salvinsalvin: a biocyclic diterpenoid; from sage and rosemary (Lamiaceae)abietane diterpenoid;
carbotricyclic compound;
catechols;
monocarboxylic acid
angiogenesis modulating agent;
anti-inflammatory agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
food preservative;
HIV protease inhibitor;
plant metabolite
toxoflavintoxoflavin : A pyrimidotriazine that is 1,6-dimethyl-1,5,6,7-tetrahydropyrimido[5,4-e][1,2,4]triazine with oxo groups at positions 5 and 7.

toxoflavin: azapteridine antibiotic; structure
carbonyl compound;
pyrimidotriazine
antibacterial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
toxin;
virulence factor;
Wnt signalling inhibitor
methyl alpha-d-galactopyranosidemethyl alpha-D-galactoside : An alpha-D-galactoside having a methyl substituent at the anomeric position.

methyl-galactopyranoside: structure in first source
alpha-D-galactoside;
methyl D-galactoside;
monosaccharide derivative
methyl beta-galactosidemethyl beta-D-galactoside : A beta-D-galactopyranoside having a methyl substituent at the anomeric position.

methyl beta-galactoside: RN given refers to (beta-D)-isomer

methyl galactoside : A methyl glycoside in which the H of the OH group on C-1 of galactose is replaced by a methyl group.
beta-D-galactoside;
methyl D-galactoside;
monosaccharide derivative
thiodigalactosidethiodigalactoside: RN given refers to beta-D-galactopyranoside (D-Gal)-isomer
methyl lactosidebeta-D-Gal-(1->4)-beta-D-Glc-OMe : A methyl glycoside comprising methyl beta-D-glucoside having an beta-D-galactosyl residue at the 4-position.disaccharide derivative;
methyl glycoside
6-n-tridecylsalicylic acid6-n-tridecylsalicylic acid: structure given in first sourcehydroxybenzoic acid
fixb protein, e colialpha-D-mannose : D-Mannopyranose having alpha-configuration at the anomeric centre.

alpha-D-mannoside : Any mannoside in which the anomeric centre has alpha-configuration.

muscarinic toxin 2: muscarinic agonists from Dendroaspis angusticeps; amino acid sequence given in first source
D-mannopyranoseepitope
cercosporincercosporin : An organic heterohexacyclic compound that is perylo[1,12-def][1,3]dioxepine-6,11-dione substituted by hydroxy groups at positions 5 and 12, by methoxy groups at positions 7 and 10, and by 2-hydroxypropyl groups at positions 8 and 9 (the R,R-stereoisomer). It is a phytotoxin which was first isolated from the pathogenic soybean fungus, Cercospora kikuchii and later found in multiple members of the genus Cercospora.

cercosporin: phyytotoxin from Cercospora beticola Sacc; posses photodynamic action on mice, bacteria & plants
n-acetyllactosamineN-acetyllactosamine : A beta-D-galactopyranosyl-(1->4)-N-acetyl-D-glucosamine having beta-configuration at the reducing end anomeric centre.

N-acetyllactosamine: RN given refers to D-isomer
beta-D-Galp-(1->4)-D-GlcpNAc
galactosealpha-D-galactoside : Any D-galactoside having alpha-configuration at its anomeric centre.D-galactopyranosemouse metabolite
LSM-42773aromatic ketone
etodolac, (-)-isomer(R)-etodolac : The R-enantiomer of etodolac. It is inactive, in contrast to the enantiomer, (S)-etodolac, which is a preferential inhibitor of cyclo-oxygenase 2 and a non-steroidal anti-inflammatory. The racemate is commonly used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain.etodolac
galactalgalactal: RN given refers to cpd with unspecified isomeric designation; structureanhydrohexose;
glycal
5,6-dehydrokawain5,6-dehydrokawain: from Alpinia speciosa rhizoma; RN given for cpd without isomeric designation; structure given in first source2-pyranones;
aromatic ether
rifamycin svrifamycin SV : A member of the class of rifamycins that exhibits antibiotic and antitubercular properties.

rifamycin SV: RN given refers to parent cpd; structure in Merck Index, 9th ed, #8009
acetate ester;
cyclic ketal;
lactam;
macrocycle;
organic heterotetracyclic compound;
polyphenol;
rifamycins
antimicrobial agent;
antitubercular agent;
bacterial metabolite
ucn 1028 ccalphostin C: structure given in first source; isolated from Cladosporium cladosporioides
abt-737aromatic amine;
aryl sulfide;
biphenyls;
C-nitro compound;
monochlorobenzenes;
N-arylpiperazine;
N-sulfonylcarboxamide;
secondary amino compound;
tertiary amino compound
anti-allergic agent;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
pf-2545920
pf-562,271indoles
meiogynin ameiogynin A: from the bark of Meiogyne cylindrocarpa; structure in first source
apogossypoloneapogossypolone: has antineoplastic activity; structure in first source