Phenotypic and functional evaluation of suppressor cells in normal pregnancy and in chronic aborters

Abstract

To evaluate the potential role of immunoregulatory cells modulating the maternal immunologic response during pregnancy, we carried out phenotypic and functional studies in patients with normal obstetrical histories during each trimester and in patients with chronic idiopathic spontaneous abortions. Using monoclonal antibodies (Ortho), total numbers of T cells (T3 +) and T4 + cells progressively increased during pregnancy (compared to nonpregnant controls) and then declined in the third trimester. Increased percentages of T8+, T10+, and Ia+ cells were found in the third trimester. The relative decline in numbers of T4+ cells, with increased numbers of T8+ cells, led to a significantly reduced T4/T8 ratio in the third trimester. Histamine receptors on T cells were quantitated by an immunofluorescent technique. Significantly reduced numbers of H 1-type receptors were noted during the second trimester of pregnancy and this was associated with a decreased H 1/H 2 ratio. Functionally, histamine-induced suppression was measured in a lymphocyte proliferation assay. Patients in the first and second trimester of pregnancy had greater histamine-induced suppression of phytohemagglutinin (PHA)-stimulated proliferation at high concentrations of histamine (10 −3 to 10 −7) but less suppression at the lower concentrations (10 −9 to 10 −11 M), compared to nonpregnant controls. In contrast, patients studied in the third trimester failed to respond to any concentration of histamine. MLC-induced suppressor activity was generated by incubating the maternal cells with either paternal or third-party mononuclear cells for 2 or 6 days and assaying the cell-free supernatant for its suppressive effects on PHA-stimulated proliferation. Maternal responses to paternal cells did not result in significant suppression in 2-day supernatants during any trimester but by 6 days the suppressive activity was equivalent to nonpregnant controls in patients during the first and second trimester. Maternal responses to third party cells was greater during the second trimester than either the first or third trimesters in both 2- and 6-day supernatants. Patients with histories of chronic idiopathic spontaneous abortions, who were not pregnant at the time of study, exhibited normal numbers of T-cell subsets and T4/T8 ratios. Numbers of both H 1 and H 2 receptor bearing T cells were proportionally reduced, resulting in a normal H 1/H 2 ratio. Despite having decreased numbers of H 1 and H 2 receptor bearing cells, histamine-induced suppression of PHA-stimulated proliferation was comparable to nonpregnant controls over the concentration range (10 −3 to 10 −11 M) employed. MLC-induced suppressor activity against paternal antigens was significantly decreased in 2-day supernatants but normal activity was detected at 6 days. Furthermore, maternal responses to third party antigen were intact. In conclusion, pregnancy appears to be characterized immunologically by a generalized increase in activated “early” T cells that may be of suppressor origin. These findings may be secondary to the presence of the fetal allograft and the problems associated with containing rejection. Patients with idiopathic spontaneous abortion do not appear to have any obvious defect in immunoregulation.