Details for: CL0001043

Cell ID: CL0001043

Cell Name: activated CD4-positive, alpha-beta T cell, human

Description: This cell type is compatible with the HIPC Lyoplate markers for 'activated CD4+ T cell', but includes via logical inference from its parent additional markers known to be expressed on activated CD4+ T cells. The inclusion of HLA-DRA in the definition restricts this definition to human activated CD4+ T cells, as activated mouse T cells do not express MHC class II.

Synonyms: activated CD4-positive, alpha-beta T lymphocyte, human, activated CD4-positive, alpha-beta T-cell, human, activated CD4-positive, alpha-beta T-lymphocyte, human, activated CD4+ T cell

Selected Context(s): Overall

Gene Significance Landscape

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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 CD4-positive, alpha-beta T cell, human 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 CD4-positive, alpha-beta T cell, human. 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 CD4-positive, alpha-beta T cell, human. 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 CD4-positive, alpha-beta T cell, human. 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 CD4-positive, alpha-beta T cell, human (CL0001043)

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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 An [activated CD4-positive, alpha-beta T cell](/details-cell/CL0001043) is a differentiated lymphocyte central to orchestrating the adaptive immune response in humans. The gene significance profile for this cell type, based on expression specificity (**Overall**), is overwhelmingly dominated by genes related to high metabolic output, robust protein synthesis, and active cell division. Top markers such as [TPT1](/details-gene/7178) and multiple mitochondrial components suggest a cellular state primed for rapid clonal expansion and the production of effector molecules following antigen recognition. The profile is consistent with a cell that has transitioned from a quiescent state to one of high biological activity to meet the demands of an active immune response. ## Key Characteristics and Function The functional identity of the activated [CD4-positive, alpha-beta T cell](/details-cell/CL0001043) is underscored by several clusters of specifically expressed genes. * **High Metabolic Activity:** A defining feature is the prominent expression of genes critical for cellular energy production. This includes multiple components of the mitochondrial electron transport chain and ATP synthase, such as [COX7C](/details-gene/1350), [ATP5F1E](/details-gene/514), [UQCRB](/details-gene/7381), and [ATP5MG](/details-gene/10632). This signature indicates a heavy reliance on oxidative phosphorylation to generate the substantial ATP required to fuel proliferation, cytokine synthesis, and other effector functions. * **Robust Protein Synthesis and Translation:** The cell is characterized by high-level expression of machinery for protein synthesis. Key markers include translationally controlled tumor protein ([TPT1](/details-gene/7178)) and multiple eukaryotic translation elongation factors ([EEF1B2](/details-gene/1933), [EEF1D](/details-gene/1936)). This is further supported by the specific expression of [NPM1](/details-gene/4869), involved in ribosome biogenesis, and [PABPC1](/details-gene/26986), a poly(A)-binding protein essential for mRNA stability and translation. This molecular machinery is essential for the rapid production of cytokines and other proteins required for its immunomodulatory roles. * **Immune Signaling and Regulation:** The cell's function in immune communication is highlighted by specific markers. The high significance of Beta-2-microglobulin ([B2M](/details-gene/567)) and the non-classical MHC class I molecule [HLA E](/details-gene/3133) suggests an important role for MHC class I-mediated interactions, potentially in regulating the activity of [Natural Killer cells](/details-cell/CL0000623) or cytotoxic T lymphocytes. Furthermore, the expression of Lymphotoxin Beta ([LTB](/details-gene/4050), [Link](https://doi.org/10.1016/0092-8674(93)90574-a)), a member of the TNF superfamily, points to its direct role in inflammation and the structural organization of secondary lymphoid tissues. The anti-proliferative gene [BTG1](/details-gene/694) is also a top marker, suggesting the presence of intrinsic negative feedback mechanisms to control the extent of T-cell expansion. The cell's identity is sharpened by its lack of expression of lineage-defining genes for other lymphocytes. For example, the strong negative significance for [CD8B](/details-gene/926) confirms its identity as a CD4-positive helper T cell, distinct from the [CD8-positive, alpha-beta T cell](/details-cell/CL0000625) cytotoxic lineage. ## Clinical Significance and Contextual Roles The gene profile provides insights into the cell's role in both normal immunity and pathology. The high metabolic state is a known therapeutic target, with drugs that inhibit metabolic pathways being explored for autoimmune diseases and cancer. The specific expression of [LTB](/details-gene/4050) directly implicates this cell type in the formation of tertiary lymphoid structures, which can sustain chronic inflammation in autoimmune diseases but also contribute to anti-tumor immunity. The prominence of [NPM1](/details-gene/4869) highlights the fundamental importance of ribosome biogenesis for T-cell expansion; mutations in [NPM1](/details-gene/4869) are a known driver of acute myeloid leukemia, underscoring its role as a master regulator of proliferation. Similarly, the high specificity of iron metabolism genes like [FTH1](/details-gene/2495) and [FTL](/details-gene/2512) suggests that iron availability is a critical checkpoint for T-cell activation, a process that can be dysregulated in various inflammatory conditions. The presence of [B2M](/details-gene/567) as a top marker is also clinically relevant, as mutations in this gene are a mechanism of tumor immune escape from T-cell mediated cytotoxicity. ## Potential Mechanisms and Research Directions 1. **Hypothesis: [BTG1](/details-gene/694) acts as a crucial checkpoint to temper T-cell proliferation and promote differentiation.** * **Surprising Findings:** The high expression specificity of [BTG1](/details-gene/694) ([CSI (Z-SCORE): 33.56](/details-gene/694)), a gene known for its anti-proliferative effects ([Link](https://doi.org/10.1002/j.1460-2075.1992.tb05213.x)), is paradoxical in a cell type defined by rapid expansion. This suggests its role is not to prevent activation, but rather to modulate it. * **Testable Questions:** Does the timing of [BTG1](/details-gene/694) expression peak after the initial proliferative burst in activated [CD4-positive, alpha-beta T cells](/details-cell/CL0001043)? Would a conditional knockout of [BTG1](/details-gene/694) in T cells lead to exaggerated expansion and a failure to contract the T-cell population or differentiate into memory cells following an immune challenge? 2. **Hypothesis: Activated [CD4-positive, alpha-beta T cells](/details-cell/CL0001043) utilize the non-classical MHC-I molecule [HLA E](/details-gene/3133) to protect themselves from cytotoxic lymphocytes and regulate the local immune response.** * **Surprising Findings:** While CD4+ T cells are defined by their interaction with MHC-II, the high specificity of MHC-I components [B2M](/details-gene/567) and particularly [HLA E](/details-gene/3133) suggests a significant, defining role for MHC-I pathway interactions in this cell's function. This may involve self-preservation in a highly inflammatory environment populated by cytotoxic cells. * **Testable Questions:** Does blocking the interaction between [HLA E](/details-gene/3133) on activated [CD4-positive, alpha-beta T cells](/details-cell/CL0001043) and its receptor (NKG2A) on [Natural Killer cells](/details-cell/CL0000623) or [CD8-positive, alpha-beta T cells](/details-cell/CL0000625) lead to increased killing of the CD4+ T cells in a co-culture system?