Maternal microchimerism and cell‐mediated immune‐modulation enhance engraftment following semi‐allogenic intrauterine transplantation

Successful intrauterine hematopoietic cell transplantation (IUT) for congenital hemoglobinopathies is hampered by maternal alloresponsiveness. We investigate these interactions in semi-allogenic murine IUT. E14 fetuses (B6 females × BALB/c males) were each treated with 5E+6 (B6) or paternal (BALB/c) bone marrow cells and serially monitored chimerism (>1% engraftment), trafficked immune cells, responsiveness to donor cells. A total of 41.0% IUT recipients (mIUT) chimeras (mean 3.0 ± 1.3%) versus 75.0% (pIUT, 3.6 1.1%). Chimeras showed higher microchimerism CD4, CD8, CD19 than non-chimeras. These minimal B6 stimulation. To interrogate tolerance, mIUT injected postnatally cells/pup; pIUT received IUT-treated pups no changes fetal levels compared controls. Donor-specific IgM IgG expressed 1%-3% recipients. splenocytes greater proliferation regulatory T (Treg) upon stimulation, while stimulation upregulated the pro-inflammatory cytokines more BALB/c. produced identical Treg cytokine responses activity lower expression exposure In contrast, naïve demonstrated alloresponsiveness Thus pIUT, associated increased trafficking, modulates Treg, efficiently mIUT, resulting improved engraftment. Paternal may be considered alternatively postnatal induce tolerance maintain