Heterogeneity in Fetal Immunocompetence during the Second Trimester of Gestation

Objective: To address the role that alloreactivity may play and better define the window for histoincompatible stem cell transplantation in utero. Subjects, Material and Methods: We studied 9 fetal blood specimens obtained by cardiocentesis during elective abortions in the second trimester by multicolor flow cytometry and in vitro stimulation. Results: Lymphocytes ranged from adult levels (3/9) to >90% leukocytes. Six specimens had T cells within adult range. T cells in the other specimens were reduced, while B cells were conversely elevated. This variability did not correlate with gestational age, or leukocyte composition. Following 4 h of mitogenesis, fetal CD4+ and CD8+ T cells from 1 of 5 specimens showed a response similar to that of maternal T cells, while the other 4 specimens showed a diminished response (0.3 ± 0.2-fold). This heterogeneity did not correlate with gestational age, or lymphocyte subset distribution. Following 18 h of in vitro mitogenesis, fetal T cells from 2 specimens showed a response similar to that of maternal T cells (0.8 ± 0.2-fold). Despite that, one specimen gave a 3-fold greater response in a one-way mixed lymphocyte reaction vs. maternal cells compared to the other specimen. Conclusion: We determine that fetal immunocompetence differs greatly during the second trimester and assessment of host vs. donor reactivity prior to in utero transplantation is likely to potentiate more favorable outcomes.