Effects of paternal lymphocyte immunization on peripheral Th1/Th2 balance and TCR V beta and V gamma repertoire usage of patients with recurrent spontaneous abortions

PROBLEM: The mechanism of immunotherapy for patients with recurrent spontan eous abortions is not well understood. In order to investigate the suppress or mechanism of paternal lymphocyte immunization, we examined peripheral bl ood lymphocyte subpopulations and the repertoire of T-cell receptor (TCR) g ene segments. METHOD OF STUDY: Twelve patients with recurrent miscarriage were treated wi th immunization with paternal lymphocyte vaccinations three times during 12 -14 weeks. Before and 2 weeks after the final inoculation, lymphocyte subse ts and intra-cellular interferon (IFN)-gamma and/or interleukin (IL)-4 prod uction were examined by flow cytometry. TCR V beta and V gamma repertoires were examined by semi-quantitative reverse transcription-polymerase chain r eaction (RT-PCR). RESULTS: We found no significant difference in CD4/CD8 ratios, prevalence o f CD56(+) CD3(+) or CD57(+) CD3(+) cells (possible extrathymic T cells), ga mma delta T cells, and CD5(+) CD19(+) (B-1) cells. However, by in vitro act ivation with phorbol 12-mytistate 13-acetate (PMA) and ionomycin, periphera l CD4 cells demonstrated a significant decrease of IFN-gamma-producing T he lper 1 (Th1) cells and an increase of IL-4-producing T helper 2 (Th2) cells after immunotherapy. Seven of nine patients who exhibited remarkable decre ases in Th1/Th2 ratios became pregnant within 6 months after three courses of immunotherapy, and four women delivered healthy babies, while none of th e three patients who exhibited an increased or unchanged Th1/Th2 ratio had full-term pregnancies (chi(2) < 0.0001). Further, changes in usage of TCR V beta and V gamma gene segments were observed after immunotherapy in six pa tients examined. CONCLUSION: Our findings suggest a shift of Th1-dominant to Th1-dominant st atus by vaccination might play important roles in maintaining successful pr egnancies. Induction of some T cells that utilize different TCR repertoires possibly suppresses maternal rejection reactions.