IL 4 Rhesus Macaque
Description
Biological Functions and Immune Roles
IL-4 Rhesus Macaque exhibits conserved immunological functions across primates:
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B-Cell Regulation: Enhances IgE/IgG1 secretion, MHC class II expression, and CD23 (FcεRII) upregulation .
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T-Cell Differentiation: Drives naïve CD4+ T cells toward Th2 phenotypes, promoting anti-parasitic and allergic responses .
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Innate Immunity: Activates mast cells, eosinophils, and monocytes while stimulating epithelial cell proliferation .
Key Functional Data:
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PBMC Stimulation: PMA/ionomycin-treated rhesus PBMCs secrete 95.34 pg/mL IL-4, compared to 47.30 pg/mL in cynomolgus macaques .
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Cytokine Correlations: Elevated IL-6, IP-10, and MCP-1 during SFTSV infection correlate with activated CD4+/CD8+ T cells and monocytes, highlighting IL-4’s indirect role in inflammatory cascades .
Detection and Quantification
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ELISA Kits: The Abcam SimpleStep ELISA® detects IL-4 in plasma, serum, and cell culture supernatants with a sensitivity of 2.2 pg/mL and a range of 15.6–1000 pg/mL .
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Antibodies: The QS-4 monoclonal antibody (U-CyTech) cross-reacts with rhesus, cynomolgus, and baboon IL-4, enabling flow cytometry and immunohistochemistry .
Experimental Models
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SFTSV Infection: Rhesus macaques infected with SFTSV show transient leukopenia and thrombocytopenia, with IL-4-linked Th2 responses modulating viral persistence in lymphoid tissues .
Clinical and Mechanistic Insights
Product Specs
Q&A
What is the primary biological role of IL-4 in rhesus macaque immune responses?
IL-4 in rhesus macaques serves as a pleiotropic cytokine critical for Th2 cell differentiation, B-cell activation, and IgE/IgG1 antibody production. It regulates CD23 expression on lymphocytes and monocytes and modulates myeloid-derived suppressor cells (MDSCs) during immune responses .
How is IL-4 quantified in rhesus macaque studies?
IL-4 levels are measured using sandwich-based ELISA kits validated for cross-reactivity between human and rhesus macaque IL-4 (Accession Number: P51492). These kits detect IL-4 in plasma, serum, and cell culture supernatants with a sensitivity of 5 pg/ml and a dynamic range of 5–1,600 pg/ml .
What experimental models use IL-4 in rhesus macaque research?
Key models include:
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Vaccine studies: IL-4 peaks transiently after NYVAC or SFV immunizations, correlating with Th2 responses .
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Infectious disease models: Pertussis infection induces systemic IL-6 and TNF-α but minimal IL-4, suggesting Th1/Th17 dominance .
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Immune modulation: MDSCs transiently expand post-vaccination, suppressing T-cell proliferation via arginase-1 and IL-10 .
How does IL-4 homology between humans and rhesus macaques impact translational research?
Rhesus macaque IL-4 shares ~40% amino acid identity with human IL-4, necessitating species-specific reagents (e.g., anti-rhesus IL-4 antibodies) . Cross-reactivity in ELISA kits requires validation .
| Species | IL-4 Homology (%) | Functional Specificity | Key Challenges |
|---|---|---|---|
| Human | 100 | Broad Th2 responses | Cross-reactivity in NHP studies |
| Rhesus | ~40 | Species-restricted activity | Limited commercial reagents |
| Mouse | ~45 | Distinct T-cell regulation | Poor cross-species applicability |
How do IL-4 responses differ between vaccine and infection models in rhesus macaques?
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Vaccine responses: IL-4 peaks transiently after NYVAC boosts, declining within weeks .
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Infection models: Pertussis infection shows negligible IL-4 elevation, favoring Th1/Th17 cytokines like IL-6 and TNF-α .
This dichotomy highlights IL-4’s context-dependent role in immune polarization.
What methodological challenges arise when interpreting IL-4 data in rhesus macaque studies?
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Cross-reactivity: ELISA kits detecting both human and rhesus IL-4 require validation for specificity .
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Temporal dynamics: IL-4 peaks rapidly post-vaccination but declines, necessitating frequent sampling .
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Tissue-specific responses: MDSCs transiently infiltrate vaccine sites but not lymph nodes, complicating systemic vs. local IL-4 effects .
How can IL-4 be optimized in rhesus macaque models for HIV/SIV vaccine development?
IL-4’s role in Th2 skewing may counteract Th1-biased responses critical for SIV/HIV control. Strategies include:
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Co-stimulatory molecules: Enhancing CD28/CD95 signaling to balance Th2 and Th1 responses .
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PD-1 blockade: Targeting Tfh cells (PD-1hiCD4+), which express Bcl6 and ICOS, to modulate IL-4-driven B-cell help .
Why do IL-4 responses vary between rhesus macaque and human vaccine trials?
How to reconcile reports of IL-4’s transient vs. persistent effects in rhesus macaque studies?
IL-4’s short half-life (~15 kDa) explains rapid clearance post-vaccination . Persistent Th2 responses may involve alternative mediators (e.g., IL-13) or memory B-cell activation .
Why does pertussis infection suppress IL-4 despite MDSC expansion?
Pertussis-induced MDSCs upregulate IL-10 and arginase-1 but not IL-4, favoring Th1/Th17 responses . This contrasts with vaccine-induced MDSCs, which may transiently secrete IL-4 to regulate inflammation .
Optimizing IL-4 detection in rhesus macaque samples
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ELISA protocol: Use 2-fold serum/plasma dilutions and validate with recombinant rhesus IL-4 standards .
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Timing: Sample at 24–48 hours post-vaccination/infection to capture IL-4 peaks .
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Controls: Include human IL-4 standards to assess cross-reactivity .
Integrating IL-4 with multi-cytokine profiling
Future Research Directions
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Epigenetic regulation: Investigate IL-4 promoter methylation in rhesus macaque T cells during SIV infection.
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Single-cell profiling: Map IL-4-producing cells (e.g., Th2, Tfh) using scRNA-seq in vaccine vs. infection models.
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Therapeutic targeting: Test IL-4 blockade to enhance Th1 responses in HIV vaccines or IL-4 agonists in allergy models.
Product Science Overview
IL-4 is a monomeric protein with a molecular weight ranging from approximately 13 kDa to 18 kDa . The recombinant version of IL-4 from Rhesus Macaque is produced in E. coli and is a single, non-glycosylated polypeptide chain containing 129 amino acids, with a molecular mass of 14.9 kDa . The mature rhesus IL-4 shares 97%, 93%, and 93% amino acid sequence identity with baboon, chimpanzee, and human IL-4, respectively .
IL-4 exerts its effects through two receptor complexes, primarily influencing the differentiation of naive helper T cells (Th0 cells) to Th2 cells . It is involved in the stimulation of activated B-cell and T-cell proliferation, and the differentiation of B cells into plasma cells. IL-4 also enhances the secretion and cell surface expression of IgE and IgG1 .
The recombinant IL-4 is produced using E. coli expression systems and is purified through proprietary chromatographic techniques . The protein is typically lyophilized from a 0.2 μm filtered solution in PBS with BSA as a carrier protein. The carrier-free version does not contain BSA, which is recommended for applications where the presence of BSA could interfere .
The recombinant IL-4 is shipped at ambient temperature and should be stored at -20 to -70 °C upon receipt. It is stable for 12 months from the date of receipt when stored as supplied. After reconstitution, it should be stored under sterile conditions at 2 to 8 °C for up to 1 month or at -20 to -70 °C for up to 3 months .
