Immunological responsiveness to Escherichia coli during pregnancy

To determine whether immunological responsiveness to a bacterial antigen is altered during pregnancy and lactation, Swiss mice (gestation, 19 to 21 days) were studied during early, middle, and late pregnancy and in the early postpartum period. Pregnant and nursing mice, each along with a virgin female littermate control, were injected with 2 x 10(6) heat-killed Escherichia coli and sacrificed 4 days later for the enumeration of splenic anti-E. coli plaque-forming cells (PFC). For 72 4- to 10-day pregnant and control mice ranked together, total PFC per spleen ranged from 0 to 312,650, with 61% of the counts from pregnant animals ranking above the median of 12,700. The mean number of PFC for the pregnant animals was greater than for sister controls in 19 of 23 litters studied (P = 0.001). Responsiveness was also increased for 72 mice tested in later pregnancy. Counts of PFC of 72% of mice 11 to 18 days pregnant were above the median when ranked with those of their controls (P < 0.001). In 18 of 21 litters studied, pregnant animals responded better than littermate controls (P = 0.001). Responses of mice at term (19 to 21 days) were depressed when compared with those of controls, but nursing animals 6 to 9 postpartum responded like virgin animals. Previous studies suggested that low concentrations of estradiol stimulate the mitosis of PFC. To determine if progesterone also increases numbers of PFC, concentrations in a range physiological for pregnancy were added to cultures of spleen cells from male mice injected with E. coli 3 days before. After 24 h of incubation, numbers of PFC in these suspensions were compared to those of the same suspensions incubated without hormone. In 19 of 25 and 48 of 68 suspensions tested at concentrations of 500 pg and 50 ng of progesterone per ml, the numbers of PFC were increased over those of the same suspensions without hormone (P < 0.01). Geometric mean number of PFC for progesterone-treated cells was 45% greater than that for the controls. Findings suggest that female sex hormones, important for the normal growth and differentiation of fetal cells, may also enhance division and/or maturation of immunocompetent cells in the mother.