Fetal Lymphocytes in the Maternal Blood

Abstract

The fluorescence of the human Y chromosome after staining with quinacrine derivatives was used in an attempt to determine the prevalence of XY lymphocytes presumptively emanating from male fetuses in the blood of pregnant women. Seven women who subsequently gave birth to male infants had 0.03%-0.20% lymphocytes with a Y body. In two women pregnant with male fetuses, no Y bodies were detected. Of 12 women who gave birth to girls, eight had no Y bodies. In the remaining four, fluorescent spots were interpreted as Y bodies. One of those women had previously had an abortion. In the remaining three cases, it was found in retrospect that the fluorescent spots emanated from exceptionally brightly fluorescent autosomal regions in the maternal or paternal chromosomes, or both. Phytohemagglutinin-stimulated and unstimulated lymphocytes showed similar frequencies of Y body. Based on determinations of the incidence of Y body-containing lymphocytes in males (35%-66.5%), it was estimated that approximately 0.1%-0.5% of lymphocytes in the blood of most women pregnant with a male fetus are of fetal origin. This figure is remarkably high, since it exceeds in relative terms that of fetal erythrocytes (which mostly appear in the mother’s blood at the time of delivery) by several orders of magnitude. It is suggested that fetal lymphocytes actively cross the feto-maternal barriers. This phenomenon may have a profound influence on the immunologic interactions between fetus and mother. The method described may not turn out to be profitable in the assessment of the fetal sex, since its accuracy may be of the order of only 80%-95%. Moreover, several limitations prevail.

Quantification of all fetal nucleated cells in maternal blood in different cases of aneuploidies

“…We have observed a relatively high number of FNCs in all pregnancies with a trisomy 18 fetus. However, the total number of FNCs was statistically not higher (p ¼ 0.1570, Mann-Whitney Rank test) for pregnancies with 47,XY,þ18 (median 7; range [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] than that observed in normal male pregnancies as reported in our previous study (median 4; range 2-6) (1). Moreover, we compared the total number of FNCs observed in trisomy 18 vs the ones observed in trisomy 21 (data obtained from 16 women carrying male trisomic 21) (26).…”

“…Moreover, we compared the total number of FNCs observed in trisomy 18 vs the ones observed in trisomy 21 (data obtained from 16 women carrying male trisomic 21) (26). The total number of FNCs was not significantly higher (p ¼ 0.1568, Mann-Whitney Rank test) in the unit volume of maternal blood of women carrying male trisomic 21 fetus (median 10; range 6-32) than in the same volume of blood of women bearing fetus with trisomy 18 (median 7; range [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

“…Fetomaternal cell traffic was first recognized in 1893 when Schmorl (3), a German pathologist, identified trophoblast cells trapped in the lung capillaries of 14 of 17 women dying of eclampsia. Walknowska et al (4) in 1969 reported the presence of XY mitogen-stimulated lymphocytes in maternal blood of pregnant women carrying male fetuses, and others confirmed this finding (5)(6)(7)(8). Herzenberg et al (9) successfully recovered fetal leukocytes from maternal blood using fluorescence-activated cell sorting (FACS) with antibodies against paternally derived HLA antigens.…”

Method of separation and concentration of fetal nucleated red blood cells in maternal blood and its application to fetal diagnosis

“…Mixing of fetal cells in the maternal circulatory system has been known from Rh-incompatible pregnancy and amniotic fluid embolism for a long time (Schroder 1975). However, it has been difficult to isolate fetal cells in maternal circulation by morphological techniques.…”

The Activation of Fetal Lymphocytes

“…The question of the placental transfer of blood cells to the fetus has not been fully settled (Benirschke & Sullivan 1970). However, it has recently been shown that a considerable number of fetal lymphocytes actively cross the placental barrier and appear in the maternal blood during pregnancy, and this traffic may very well turn out to be a twoiway one (Schroder & de la Chapelle 1972). A number of authors have reported similar spontaneous transformation rates for fetal and adult cells (Jones 1969, Prindull 1971), but they studied the cells after over 70 h in culture and the present investigation indicates that the spontaneous thymidine incorporation decreases with an increasing period of culture in vitro.…”