Modulation Of T Cell Function By Coagulation Factor Xa

The serine protease factor Xa (FXa) plays an integral role in the coagulation cascade and has recently been implicated in a variety of proinflammatory roles, establishing it as a link between coagulation and inflammatory processes. In this thesis, I elaborate on previous literature by characterizing further the response of primary human T lymphocytes to FXa. Building on previous literature that describes the effect of FXa on whole T cell populations, I describe here the effect of FXa on both antigen-independent and antigen-dependent proliferation and costimulation of primary CD4+ and CD8+ T cells, thereby establishing an immunological role for FXa. Further, I show that FXa elicits an immediate and direct effect on T cells demonstrated by the rapid upregulation of the signalling cascade kinases, ERK1 and ERK2. Lastly, I demonstrate that the protease activated receptor 2 (PAR2) is involved in the mediation of this direct FXa effect.