Immunity & infection
Humanized mice engrafted only with human hematopoietic stem cell (HSC) do not develop fully functional T-cells. The BLT mouse model, which consists of co-implanting HSC from fetal liver with autologous fetal thymic tissue, was developed to promote an optimal T-cell reconstitution and maturation. However, access to human fetal tissues is challenging both from the ethical point of view and logistic. The goal of our study was to find an alternative to the use of fetal tissues to create a humanized mouse model with functional T-cells. Methods. We used pediatric thymus excised during cardiac surgeries (CS thymus) combined with umbilical cord blood CD34+ cells (CCST mice). CS thymuses pieces were implanted in the quadriceps of an NSG mouse, after being put in culture Results. CCST mice exhibited a significant engraftment of T-cells, compared to humanized mice without thymus (p<0.0001). T-cells from both CCST and BLT mice showed a similar function as evaluated by proliferation assays upon PHA stimulation ex vivo and rejection of allogeneic leukemic cells lines in vivo. CCST mice were susceptible to HIV-1 infection via mucosal or intraperitoneal route, as shown by detectable viral load, HIV DNA and p24+ cells, at similar levels to those of BLT mice. Importantly, CCST mice displayed more effective ex vivo HIV-1-specific T-cell responses compared to BLT (p<0.0001 for CD8+cells, p<0.01 for CD4+cells). Conclusions. CCST mice represent an alternative to the regular BLT mouse model. Those easy-to-access thymuses can be used to generate a large number of mice compared to fetal thymuses.