Maternal cytotoxic T cell responses to fetal antigens during and after pregnancy

During human pregnancy there is the ‘transplacental traffic’of fetal cells into the maternal circulation. These cells can persist for decades, a phenomenon termed ‘fetal microchimerism’. Exposure to fetal cells may provoke a maternal cellular immune response. The impact this has on the mother's health remains unclear but associations have been suggested between fetal microchimerism and autoimmune disease and recurrent spontaneous abortion. This study investigates, in a preliminary cohort, the development and characteristics of the maternal cellular immune response to fetal antigen during and after pregnancy. Preliminary results show maternal cytotoxic T cell responses against fetal antigen can be detected utilising ‘dextramer’ based techniques and flow cytometry. 44 women with 2 or more sons were screened, 17 were the required human leucocyte antigen type (A2 or B7). Fetal specific T cells were detected in 41% of these 17 women, even 34 years after pregnancy. A preliminary but novel finding is that these responses were also detected during pregnancy. Furthermore, T cell clones specific for fetal cells have been isolated from peripheral blood during and after pregnancy. The functional characteristics of these fetal specific T cell clones can then be studied. The fetal specific T cell clones are cytotoxic (>50% killing at a 1:1 ratio) and release interferon y (IFNy) (mean 1600 pg/ml IFNy) in response to fetal antigen. Cytotoxic maternal T cell responses to fetal antigen are therefore common after pregnancy and can also be detected during pregnancy itself. Understanding this phenomenon may offer insights into the immunobiology of pregnancy and fields such as autoimmunity and transplantation biology.