Phenotypic and functional evaluation of suppressor cells in normal pregnancy and in chronic aborters.
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 H1-type receptors were noted during the second trimester of pregnancy and this was associated with a decreased H1/H2 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 non-pregnant 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 H1 and H2 receptor bearing T cells were proportionally reduced, resulting in a normal H1/H2 ratio. Despite having decreased numbers of H1 and H2 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.(ABSTRACT TRUNCATED AT 400 WORDS)
D000026:Abortion, Habitual / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011247:Pregnancy; D011968:Receptors, Histamine / Q000502:physiology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D011968:Receptors, Histamine