Preclinical humanized CD4 mouse model
The human CD4 mouse model allows in vivo efficacy and safety assessment of anti-human CD4 compounds.
hCD4 features
- No expression of murine CD4
- No physiological deregulation: Unaltered immune cell distribution, and T helper cell activity
- Unaltered immune response and T-helper activity in CD4 humanized mice
Validation
Human CD4 replaces murine CD4. Homozygous CD4 humanized mice display human-CD4 expression in PBMC. No murine CD4 expression is observed.
Blood samples from wild-type and homozygous CD4 humanized mice stained with a combination of mAbs (anti-murine CD4, anti-human CD4) and analyzed by flow cytometry.
Unaltered immune cell distribution. Homozygous CD4 humanized mice display same frequencies of B cells, NK cells and T cells in spleen.
Splenocytes are stained with different mAb combinations to assess frequencies of lymphocyte subsets measured by flow cytometry. Grey bars represent values for wild-type mice and hatched bars represent values for CD4 humanized mice.
Conserved cytokine expression profile. Homozygous CD4 humanized mice display similar cytokine expression after ConA stimulation.
IL-2, IFN-γ and IL-4 concentrations in culture supernatants of mouse splenocytes stimulated with Con A are measured by using a 3-Plex Luminex kit. Black bars represent values for wild-type mice and hatched bars represent data for CD4 humanized mice.
Similar Ig production. Homozygous CD4 humanized mice display similar anti-KLH isotyping to wild-type mice.
Anti-KLH specific IgG1, and IgG2b polyclonal antibodies are assessed by sandwich ELISA in the serum of mice at day 28 after immunization with KLH and CFA. Serum samples from wild-type (WT) or homozygous CD4 humanized mice (HO CD4) were tested at different dilutions plotted against OD values.
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Preclinical humanized CD4 mouse model
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