Details for: CL0000906

Cell ID: CL0000906

Cell Name: activated CD8-positive, alpha-beta T cell

Description: A CD8-positive, alpha-beta T cell with the phenotype CD69-positive, CD62L-negative, CD127-negative, CD25-positive, and CCR7-negative.

Synonyms: activated CD8-positive, alpha-beta T lymphocyte, activated CD8-positive, alpha-beta T-cell, activated CD8-positive, alpha-beta T-lymphocyte

Selected Context(s): Overall

Gene Significance Landscape

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Score:
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Genes

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Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for activated CD8-positive, alpha-beta T cell within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for activated CD8-positive, alpha-beta T cell. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for activated CD8-positive, alpha-beta T cell. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for activated CD8-positive, alpha-beta T cell. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

Maximum number of selected genes.
Select a context for the baseline cell.
Select a context for the target cell.
Target Cell for CSI:  activated CD8-positive, alpha-beta T cell (CL0000906)

 Legend
Nodes (Genes):
 Query Gene
Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
 Very High
 High
 Medium
 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

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## Summary The [activated CD8-positive, alpha-beta T cell](/details-cell/CL0000906) is a cytotoxic lymphocyte characterized by the surface phenotype CD69-positive, CD62L-negative, CD127-negative, CD25-positive, and CCR7-negative. This profile indicates a cell that has recently encountered its cognate antigen and has transitioned into an effector state. The gene significance landscape is dominated by markers associated with T cell mediated cytotoxicity, high translational and metabolic activity, and chemokine production. The high specificity score for [B2M](/details-gene/567), a component of the MHC class I molecule, underscores its fundamental role in antigen presentation and cytotoxic function. **Overall**, the data portrays a highly active cell poised to execute effector functions while engaging intrinsic regulatory pathways to control its response. ## Key Characteristics and Function The functional profile of the [activated CD8-positive, alpha-beta T cell](/details-cell/CL0000906) is defined by several core biological themes, as revealed by its top marker genes based on expression specificity (Z-score). * **Antigen Recognition and Cytotoxicity:** The cell's identity as a cytotoxic T lymphocyte is strongly supported by the high significance of genes integral to MHC class I-mediated processes. [B2M](/details-gene/567) (Beta-2-microglobulin), the top marker, is an essential subunit of all MHC class I molecules. Similarly, [HLA E](/details-gene/3133), a non-classical MHC class I molecule, is also a significant marker, suggesting a role in both self-recognition and interaction with other immune cells like [Natural Killer cells](/details-cell/CL0000623) ([Link](https://pubmed.ncbi.nlm.nih.gov/10064069)). The presence of canonical T-cell signaling components like [PTPRC](/details-gene/5788) (CD45) and [CD3E](/details-gene/916) (part of the T-cell receptor complex) further solidifies its identity. * **High Translational and Metabolic Activity:** Activation triggers a massive demand for protein synthesis and energy. This is reflected in the prominence of genes involved in transcriptional and translational machinery. Significant markers include the transcription coregulator [BTG1](/details-gene/694), translation elongation factors [EEF1D](/details-gene/1936) and [EEF1B2](/details-gene/1933), and the poly(A)-binding protein [PABPC1](/details-gene/26986). This suggests the cell is actively transcribing and translating genes required for its effector functions, such as cytokines and cytotoxic granules. Concurrently, genes related to energy production, such as [ATP5F1E](/details-gene/514) and [COX1](/details-gene/4512), are also highly specific, indicating heightened mitochondrial activity to fuel this activated state. * **Effector Function and Immune Regulation:** The cell is primed for effector roles, as shown by the high significance of the chemokine [CCL5](/details-gene/6352), a potent chemoattractant for monocytes, T cells, and other immune cells. This indicates a key function in orchestrating the inflammatory response at sites of infection or disease. Interestingly, the anti-proliferative gene [BTG1](/details-gene/694) is one of the top markers ([Link](https://doi.org/10.1002/j.1460-2075.1992.tb05213.x)). Its high specificity in an "activated" cell suggests the concurrent engagement of intrinsic negative feedback mechanisms to control clonal expansion and prevent immunopathology. The high significance of the early activation antigen [CD69](/details-gene/969) confirms the cell's recent activation status. * **Cellular Identity Profile:** The anti-marker profile helps refine the cell's identity. The significant negative specificity of [ATP6V0C](/details-gene/527), a subunit of the vacuolar H+-ATPase, may point to a specific metabolic state or pathway that is downregulated upon activation. The lack of specificity for several common housekeeping genes like [GAPDH](/details-gene/2597) indicates that while these genes are expressed, their expression levels are not uniquely high in this cell type compared to others, and thus they do not serve as defining markers. ## Clinical Significance and Contextual Roles **Overall**, the [activated CD8-positive, alpha-beta T cell](/details-cell/CL0000906) represents a critical effector arm of the adaptive immune system, essential for clearing viral infections and eliminating cancerous cells. Its gene signature provides insights into its clinical relevance. The strong signature for cytotoxicity and inflammation ([B2M](/details-gene/567), [CCL5](/details-gene/6352)) highlights its central role in both protective immunity and immunopathology. Dysregulation of these cells can contribute to autoimmune diseases, chronic inflammation, and transplant rejection. For instance, [CCL5](/details-gene/6352) is implicated in the pathogenesis of diseases like rheumatoid arthritis and atherosclerosis by recruiting inflammatory cells to tissues. The expression of [TXNIP](/details-gene/10628), a regulator of thioredoxin and cellular redox state, suggests a link between the cell's activation state and its response to oxidative stress, a common feature of inflamed microenvironments. [TXNIP](/details-gene/10628) is also known to be involved in NLRP3 inflammasome activation, potentially connecting this T cell subset directly to innate inflammatory pathways. The high specificity of [FTL](/details-gene/2512) (Ferritin Light Chain), involved in iron storage, may also reflect an adaptive response to the high metabolic and oxidative demands of the activated state. ## Potential Mechanisms and Research Directions 1. **Hypothesis: Activated CD8 T-cells engage a concurrent transcriptional program of effector function and self-regulation.** The data reveal a paradoxical co-expression of genes driving a high-output metabolic and translational state (e.g., [EEF1D](/details-gene/1936), [PABPC1](/details-gene/26986)) alongside the highly specific expression of the anti-proliferative transcription coregulator [BTG1](/details-gene/694). This suggests that upon activation, these T cells initiate not just an effector program but also a simultaneous, intrinsic braking mechanism. This dual programming may be critical for ensuring a potent but controlled and self-limiting immune response, preventing the exhaustion or immunopathology that could result from unchecked proliferation. * **Surprising Findings:** The identification of an anti-proliferative gene, [BTG1](/details-gene/694), as a top specificity marker for a cell defined by activation is counterintuitive and suggests its role as a key checkpoint regulator. * **Testable Questions:** Does the targeted knockout of [BTG1](/details-gene/694) in [CD8-positive, alpha-beta T cells](/details-cell/CL0000906) result in a greater magnitude of proliferation following TCR stimulation, and does this lead to a more rapid onset of T-cell exhaustion? 2. **Hypothesis: Activated CD8 T-cells upregulate non-classical MHC molecules like HLA-E to modulate the local immune microenvironment, particularly NK cell activity.** The high specificity of [HLA E](/details-gene/3133), in addition to the canonical MHC-I component [B2M](/details-gene/567), suggests a specialized role beyond simple antigen presentation. [HLA E](/details-gene/3133) is a primary ligand for the inhibitory receptor NKG2A expressed on [Natural Killer cells](/details-cell/CL0000623) and a subset of activated CD8 T-cells. Therefore, its upregulation may be a mechanism by which activated T cells protect themselves from NK-cell-mediated killing, allowing the adaptive response to proceed. This creates a regulatory axis where the cell's activation status directly influences its susceptibility to innate immune surveillance. * **Surprising Findings:** The prominence of a non-classical MHC-I molecule, [HLA E](/details-gene/3133), as a key marker points to a sophisticated layer of immune regulation orchestrated by this cell, extending its influence beyond direct target cell killing. * **Testable Questions:** Does blocking the interaction between [HLA E](/details-gene/3133) on activated [CD8-positive, alpha-beta T cells](/details-cell/CL0000906) and NKG2A on NK cells lead to increased lysis of the T cells in a co-culture system?