MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-EXPRESSING ENDOTHELIAL-CELLS INDUCE ALLOSPECIFIC NONRESPONSIVENESS IN NAIVE T-CELLS

The role of endothelial cells (EC) in initiating a primary T cell resp onse is of importance in clinical transplantation and autoimmunity sin ce EC are the first allogeneic target encountered by the recipient's i mmune system and may display tissue-specific autoantigens in the conte xt of an inflammatory response. In this study, we have investigated th e antigen-presenting cell function of human umbilical vein-derived EC (HUVEC), depleted of constitutively major histocompatibility complex c lass II+ cells and induced to express class II molecules by interferon -gamma. The results show that HUVEC do not express B7 but can support proliferation by antigen-specific T cell clones. In contrast, they wer e unable to initiate a primary alloresponse using three independent HU VEC cultures and MHC class II-mismatched CD4(+) T cells from eight don ors. The response to HUVEC was reconstituted by trans-costimulation pr ovided by DAP.3 transfectants expressing human B7.1. Coculture of peri pheral blood T cells with EC expressing allogeneic DR molecules had ma rkedly different effects on CD45RO(+) and RAI subsets. Subsequent reac tivity of the RO(+) T cells was unaffected by exposure to EC, indicati ng a neutral encounter. In contrast, culture with DR(+) EC induced all ospecific nonresponsiveness in RA(+) T cells.