ABSTRACT
OBJECTIVE: The prevalence of male microchimerism (MC) in parous females, nonparous females, and parous female cancer patients was examined. MATERIALS AND METHODS: DNA extracted from peripheral blood leukocytes and male Y-chromosomal DNA was amplified using a sensitive two-stage polymerase chain reaction technique. Controls prepared by mixing human male and female cell lines demonstrated the sensitivity of the technique to be in the range of 1 male cell per 1 million female cells. RESULTS: Findings of this study showed that the percentage of MC-positive females was highly dependent on the amount of DNA analyzed; 57% of normal parous females who bore at least one son were found to have male cells in their blood when 25 mug DNA or more from the samples was analyzed. This frequency is much higher than previous reports indicating a prevalence of 33% for normal parous females. Analysis of samples obtained from 200 parous female cancer patients revealed an incidence of 34% MC(+); 7.4% of normal nonparous female controls had evidence of MC. CONCLUSION: The long-term persistence of male cells in the maternal circulation could indicate maternal immune tolerance of paternally inherited fetal antigens. This maternal tolerance might be exploited in female patients with malignant disease to deliver immune cellular therapy from their sons.
Subject(s)
Chimerism , DNA/blood , Fetomaternal Transfusion/epidemiology , Neoplasms/immunology , Parity , Adult , Aged , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Chimerism/drug effects , Chromosomes, Human, Y/genetics , Female , Fetomaternal Transfusion/blood , Fetomaternal Transfusion/immunology , Genetic Markers , Hematologic Neoplasms/blood , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Humans , Immune Tolerance , Immunotherapy , Male , Middle Aged , Neoplasms/blood , Neoplasms/drug therapy , Neoplasms/therapy , Pregnancy , PrevalenceABSTRACT
BACKGROUND: Macrophages, osteoclasts, dendritic cells, and microglia are highly specialized cells that belong to the mononuclear phagocyte system. Functional and phenotypic heterogeneity within the mononuclear phagocyte system may reveal differentiation plasticity of a common progenitor, but developmental pathways leading to such diversity are still unclear. RESULTS: Mouse bone marrow cells were expanded in vitro in the presence of Flt3-ligand (FL), yielding high numbers of non-adherent cells exhibiting immature monocyte characteristics. Cells expanded for 6 days, 8 days, or 11 days (day 6-FL, day 8-FL, and day 11-FL cells, respectively) exhibited constitutive potential towards macrophage differentiation. In contrast, they showed time-dependent potential towards osteoclast, dendritic, and microglia differentiation that was detected in day 6-, day 8-, and day 11-FL cells, in response to M-CSF and receptor activator of NFkappaB ligand (RANKL), granulocyte-macrophage colony stimulating-factor (GM-CSF) and tumor necrosis factor-alpha (TNFalpha), and glial cell-conditioned medium (GCCM), respectively. Analysis of cell proliferation using the vital dye CFSE revealed homogenous growth in FL-stimulated cultures of bone marrow cells, demonstrating that changes in differential potential did not result from sequential outgrowth of specific precursors. CONCLUSIONS: We propose that macrophages, osteoclasts, dendritic cells, and microglia may arise from expansion of common progenitors undergoing sequential differentiation commitment. This study also emphasizes differentiation plasticity within the mononuclear phagocyte system. Furthermore, selective massive cell production, as shown here, would greatly facilitate investigation of the clinical potential of dendritic cells and microglia.