Target type: biologicalprocess
The process in which a precursor cell type acquires the specialized features of a CD8-positive, alpha-beta intraepithelial T cell. Intraepithelial T cells are found among epithelial cells in mucosal areas and have distinct phenotypes and developmental pathways. [GOC:add, ISBN:0781735149]
CD8-positive, alpha-beta intraepithelial T cells (iIELs) are a specialized subset of T lymphocytes residing within epithelial tissues, primarily in the gut, skin, and lungs. Their development is a complex process involving multiple stages, influenced by both genetic and environmental factors.
1. **Commitment to the T cell lineage:** Early hematopoietic progenitors in the bone marrow commit to the T cell lineage, expressing the transcription factor *TCF-1* and migrating to the thymus for further differentiation.
2. **Thymus-dependent development:** In the thymus, T cell progenitors undergo a series of developmental stages, including double-negative (DN) stages (CD4-CD8-) and double-positive (DP) stages (CD4+CD8+). During these stages, T cells rearrange their TCR genes, undergo positive selection (selecting for cells with TCRs capable of recognizing self-MHC molecules), and negative selection (eliminating cells with TCRs recognizing self-antigens too strongly, preventing autoimmunity).
3. **Commitment to the CD8 lineage:** After positive selection, DP thymocytes commit to either the CD4 or CD8 lineage. CD8 lineage commitment is influenced by the affinity of the TCR for MHC Class I molecules, leading to downregulation of CD4 and upregulation of CD8.
4. **Migration to peripheral tissues:** Mature CD8+ T cells exit the thymus and circulate in the peripheral blood. However, a subset of these cells is destined to become iIELs.
5. **iIEL differentiation:** The differentiation of CD8+ T cells into iIELs is influenced by various factors, including:
* **Environmental signals:** The gut epithelium presents a unique environment rich in commensal bacteria, dietary antigens, and epithelial cell-derived signals. These signals trigger the expression of specific transcription factors and signaling pathways crucial for iIEL differentiation.
* **Cytokine milieu:** IL-15, IL-7, and TGF-beta are key cytokines involved in iIEL differentiation. IL-15 promotes survival and proliferation, while IL-7 and TGF-beta induce expression of lineage-specific transcription factors and effector molecules.
* **TCR stimulation:** TCR engagement with self-antigens expressed on epithelial cells contributes to iIEL differentiation.
6. **Acquisition of specialized functions:** iIELs develop unique effector functions crucial for maintaining mucosal barrier integrity and immunity. These include:
* **Cytotoxicity:** iIELs express high levels of cytotoxic molecules like perforin and granzyme B, enabling them to eliminate infected or damaged epithelial cells.
* **Cytokine production:** iIELs can produce cytokines like IFN-gamma and TNF-alpha, contributing to inflammation and immune responses.
* **Barrier maintenance:** iIELs play a role in regulating epithelial cell turnover and integrity, preventing pathogen invasion.
7. **Homeostasis and regulation:** iIELs are tightly regulated to maintain a balance between immune responses and tissue integrity. This involves intricate interactions between iIELs, epithelial cells, and other immune cells in the mucosal environment.
In summary, CD8-positive, alpha-beta iIEL differentiation is a complex process involving thymus-dependent development, migration to the periphery, and specialized differentiation in response to environmental signals, cytokine milieu, and TCR engagement. These cells play a critical role in maintaining mucosal homeostasis and defending against pathogens. '
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Protein | Definition | Taxonomy |
---|---|---|
N-arachidonyl glycine receptor | An N-arachidonyl glycine receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:Q14330] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
dronabinol | Delta(9)-tetrahydrocannabinol : A diterpenoid that is 6a,7,8,10a-tetrahydro-6H-benzo[c]chromene substituted at position 1 by a hydroxy group, positions 6, 6 and 9 by methyl groups and at position 3 by a pentyl group. The principal psychoactive constituent of the cannabis plant, it is used for treatment of anorexia associated with AIDS as well as nausea and vomiting associated with cancer chemotherapy. Dronabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. | benzochromene; diterpenoid; phytocannabinoid; polyketide | cannabinoid receptor agonist; epitope; hallucinogen; metabolite; non-narcotic analgesic |
abnormal cannabidiol | monoterpenoid | ||
sr141716 | amidopiperidine; carbohydrazide; dichlorobenzene; monochlorobenzenes; pyrazoles | anti-obesity agent; appetite depressant; CB1 receptor antagonist | |
cp-55,940 | |||
n-arachidonylglycine | N-arachidonoylglycine : Biologically active derivative of anandamide N-arachidonylglycine: structure in first source | fatty amide; N-acylglycine | |
emindole SB | terpenoid indole alkaloid | Aspergillus metabolite; marine metabolite; Penicillium metabolite |