Mitogen-stimulated lymphoid cells from human newborns suppress the proliferation of maternal lymphocytes actoss a cell-impermeable membrane.

Abstract

The immunologic consequences of the interaction between lymphocytes from human newborns and their mothers were investigated in vitro . Maternal and male baby lymphocytes were cocultured in the presence or absence of PHA, and the resulting cellular proliferation was assessed by a) the fluorescent chromosome technique with the Y chromosome as a marker for dividing male baby cells, and by b) measuring the incorporation of 3 H-thymidine in one- and two-way mixed lymphocyte cultures (MLC). In confirmation of previous reports, we found that approximately 90 to 100% of the dividing cells in two-way MLC were of baby origin, indicating that lymphocytes from human newborns effectively inhibit the proliferative capacity of maternal lymphocytes in 6-day MLC. The simultaneous measurement of 3 H-thymidine uptake in the co-cultures revealed that the maternal cells with an inhibited proliferative capacity did cause a strong allogeneic stimulation in the newborn cell population. The suppressor activity associated with newborn lymphocytes was completely abrogated by irradiation with 6000 rads, showing a requirement for cell division in the in vitro development of the anti-proliferative effect on maternal cells. In contrast to the suppressive effect mediated by actively dividing newborn lymphocytes, irradiated cells from newborns exerted a strong stimulating effect on maternal lymphocyte proliferation in one-way MLC. Experiments using a double chamber culture system showed that mitogen-stimulated cells from newborns could effectively suppress the proliferation of lymphocytes from recently delivered mothers and nonpregnant adult females across a cell-impermeable membrane. PHA-stimulated lymphocytes from nonrelated adults did not, however, inhibit the division of maternal lymphocytes or lymphocytes from another nonpregnant woman when physically separated in double chamber cultures. Furthermore, mitogen-stimulated cells from one newborn failed to inhibit the proliferation of cells from another newborn. These findings suggest that proliferating newborn cells inhibit maternal lymphocyte proliferation by releasing a low m.w.-soluble suppressive factor(s). The characterization of the inhibitory substance released from mitogen- or alloantigen-activated human newborn suppressor cells is in progress.