ENDOTHELIAL ANTIGEN PRESENTATION - STIMULATION OF PREVIOUSLY ACTIVATED BUT NOT NAIVE TCR-TRANSGENIC MOUSE T-CELLS

In vitro experiments have shown that endothelial cells can function as antigen-presenting cells to CD4(+) T lymphocytes. The studies present ed here address the question of whether naive versus previously activa ted CD4(+) helper T cells differ in their responses to endothelial ant igen presentation. TCR-transgenic mice were used as a source of naive T cells of defined antigen specificity. These cells were stimulated in vitro with antigen and splenic antigen-presenting cells to generate p opulations of T lymphocytes with a previously activated/memory phenoty pe. Two different types of mouse endothelial cells were used as antige n-presenting cells, including the SVEC4-10 line derived from lymph nod e endothelium and primary murine pulmonary microvascular endothelium, Monolayer cultures of both types of endothelium were capable of antige n-dependent stimulation of previously activated TCR-transgenic CD4(+) cells. In contrast, neither endothelial type could activate naive CD4( +) T cells. When costimulatory signals were provided in trans by the a ddition of MHC-mismatched mouse spleen cells, activation of naive T ce lls by endothelial antigen presentation could be demonstrated. The exp ression of ICAM-1 or VCAM-1 on the endothelial cells was not sufficien t to activate naive T cells. Furthermore, the mouse lung endothelium c onstitutively expresses B7-1, and therefore, the inability of endothel ium to stimulate naive T cells could not be attributed to a lack of CD 28-ligands. These studies suggest that the potential role of endotheli al antigen presentation in immune responses is restricted to promoting responses by T tells which have previously encountered antigen presen ted by other antigen-presenting cells. (C) 1098 Academic Press.