Utilising T cell receptor transgenic mice to define mechanisms of maternal T cell tolerance in pregnancy☆

Abstract 

Studies in mice demonstrate that the maternal T cell repertoire is aware of paternal antigens during pregnancy, but in healthy pregnancy reactive T cells do not mediate anti-fetal immunity. Mice expressing transgenic T cell receptors (TCRs) specific for paternal and conceptus antigens are powerful tools for elucidating the events surrounding paternal antigen presentation to the maternal T cell repertoire, the nature of the ensuing T cell response and the factors that skew the response towards immune tolerance to allow survival and development of the conceptus. While results from different transgenic TCR models are not always consistent, there is now sufficient data to allow a consensus interpretation that maternal antigen presenting cells present initially seminal fluid antigens and later placenta-derived antigens to both the CD4+ and CD8+ T cell repertoire. T cell proliferation is generally followed by entry into a state of anergy demonstrated by decreased cytokine production and hyporesponsiveness upon restimulation. Some models also demonstrate downregulation of the TCR and co-stimulatory molecules, clonal deletion of paternal antigen-reactive T cells, or alternatively T cell ignorance of paternal antigens. This review will summarise the range of transgenic TCR studies that have shed light on the events surrounding paternal antigen presentation and the various T cell responses to insemination and pregnancy. The benefits, limitations and caveats of these models, and their impact upon data interpretation, are discussed.

Abbreviations: DC, dendritic cell, APC, antigen presenting cell, OVA, ovalbumin, TCR, T cell receptor, TAP, transporter associated with antigen processing, CTL, cytotoxic lymphocyte, CFSE, carboxyfluorescein succinimidyl ester, pc, post-coitum

Keywords: Tolerance, Uterus, Pregnancy, T cell, T cell receptor, Transgenic TCR model