| Cell-mediated immune responses during pregnancy are not well understood, and the effect of pregnancy on immunologic memory is unknown. This body of work beings a systematic and quantitative investigation of T-cell responsiveness in pregnancy during the acute phase of a viral infection, generation of immunologic memory, and the recall response to a secondary challenge with the virus.; Lymphocytic choriomeningitis virus (LCMV) infection in C57BL/6 mice served as the experimental model. Adult mice infected with LCMV (Armstrong strain) will generate a potent immune response and clear the virus within 8–10 days mediated by CD8+ cytotoxic T-lymphocytes (CTL) (effector cells). Comparison of viral-specific CD8+ T cells between pregnant and nonpregnant mice included both physical and functional assessments. Major histocompatibility complex (MHC) class I tetramers were used to enumerate the antigen-specific CD8+ T-cells. Functional capability of the cells was evaluated using intracellular cytokine staining (ICS) for the presence of interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) in response to stimulation with cognate peptide. In addition, the ability to clear the virus in vivo was assessed using plaque assays for various tissues.; Our data show that there was no overall difference in the antigen-specific CD8+ T cell response between pregnant and nonpregnant mice with regards to number and function during the primary infection, memory phase, and recall response upon secondary challenge. Pregnant mice failed to clear LCMV from the uterus and placenta prior to delivery, however, despite a significant expansion of antigen-specific CD8+ T cells, systemic clearance of the virus in every other tissue assayed, and the noted presence of antigen-specific cells in the uterus and placenta prior to delivery.; In addition, pregnancy outcomes were poor. We observed a high mortality rate in the pups (69.9%), high rate of abortion (45.7%), and high maternal mortality rate (28.6%), as well as a decreased average litter size.; The findings suggest that systemic immunity is not impaired during pregnancy for a primary infection and development and function of a memory T cell pool. An understanding of immune system functioning during pregnancy has significant implications for many fields of medicine including transplantation, autoimmune disorders, cancer, and infectious disease. |
