Радиш Т. Lymphocyte functional state in women with recurrent pregnancy loss followed immunization with allogenic leukocytes.

The lymphocyte subsets, activation marker expression and activity of ConA-treated lymphocytes have been studied in 58 patients with unexplained recurrent pregnancy loss (URPL) and 22 healthy women with normal pregnancy as a control in 4-7 weeks of pregnancy. The increase of CD16/56+ cell level and CD4+/CD8+ ratio and decrease of CD19+ cell level have been found in peripheral blood of URPL patients in comparison with a control. The expression of HLA-DR was upregulated on CD3+ and CD8+ cells and the expression of CD25 was downregulated on CD3+, CD4+, CD8+ and CD16/56+ cells in URPL women. High frequency of abnormal ConA-induced stimulation and decreased suppressive activity of ConA-induced lymphocyte were found in URPL patients compared to control. Data obtained suggest disorders in feto-maternal recognition in women with URPL in early pregnancy that led to form inadequate immune response to fetus realized as deficiency of T-cytotoxic cell limitation, downregulation of TR cell generation,defect of suppressor function. Low NK activation and limitation of naive helper differentiation to memory cells in URPL women could be considered as compensative immune mechanisms. The comparison of study results of 31 URPL patients followed alloimmunization with results of 14 URPL patients followed placebo and 23 normal pregnant women showed that allogenic immunization in 5-7 weeks of pregnancy led to normalization of CD25 expression on CD4+ lymphocytes, upregulation and normalization of CD25 expression with downregulation and normalization of HLA-DR expression on CD8+ lymphocytes, upregulation and normalization of CD8 and CD25 expression on CD16/56+ cells, enhance of ConA-induced suppressor function, change abnormal stimulatory to normal inhibitory effect of ConA-induced lymphocyte 2 weeks after treatment. As a result of immunization we found normalization of B-cell level, decrease of NK level and dynamic increase of chorionic gonadotropin and glycodelin concentration in blood of URPL women. Than complete or partial normalization of peripheral blood lymphocyte subsets, lymphocyte activation and suppressor function, placental protein production has been observed as a result of treatment for recurrent pregnancy loss with allogenic immunization in early pregnancy. Our results showed low side effects and high clinical efficacy (90 %) of alloimmunization. Based on correlation analysis results, using of some parameters (HLA-DR expression on CD3+ cells, CD4+/CD8+ cell ratio and CD3-8+ cell level, ConA-induced lymphocyte activity, glycodeline concentration) were proposed for estimation of alloimmunization efficacy. Conclusion: data obtained suggest, that allogenic immunization upregulated systemic feto-maternal recognition and contributed adequate maternal immune reaction to fetus in patients with unexplained recurrent pregnancy loss through alloantigenic stimulation of lymphocytes, stimulation of TR cell generation, recovery of lymphocyte suppressor function, upregulation of NK activation, enhance of homeostatic control for T-cytotoxic cells.