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The Journal of Immunology, 2002, 169: 6154-6161.
Copyright © 2002 by The American Association of Immunologists

Mouse Vascular Endothelium Activates CD8+ T Lymphocytes in a B7-Dependent Fashion1

Daniel Kreisel*, Alexander S. Krupnick*, Keki R. Balsara*, Markus Riha*, Andrew E. Gelman*, Sicco H. Popma*, Wilson Y. Szeto*, Laurence A. Turka{dagger} and Bruce R. Rosengard2,*

Departments of * Surgery and {dagger} Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104

Despite several studies examining the contribution of allorecognition pathways to acute and chronic rejection of vascularized murine allografts, little data describing activation of alloreactive T cells by mouse vascular endothelium exist. We have used primary cultures of resting or IFN-{gamma}-activated C57BL/6 (H-2b) vascular endothelial cells as stimulators and CD8+ T lymphocytes isolated from CBA/J (H-2k) mice as responders. Resting endothelium expressed low levels of MHC class I, which was markedly up-regulated after activation with IFN-{gamma}. It also expressed moderate levels of CD80 at a resting state and after activation. Both resting and activated endothelium were able to induce proliferation of unprimed CD8+ T lymphocytes, with proliferation noted at earlier time points after coculture with activated endothelium. Activated endothelium was also able to induce proliferation of CD44low naive CD8+ T lymphocytes. Activated CD8+ T lymphocytes had the ability to produce IFN-{gamma} and IL-2, acquired an effector phenotype, and showed up-regulation of the antiapoptotic protein Bcl-xL. Treatment with CTLA4-Ig led to marked reduction of T cell proliferation and a decrease in expression of Bcl-xL. Moreover, we demonstrate that nonhemopoietic cells such as vascular endothelium induce proliferation of CD8+ T lymphocytes in a B7-dependent fashion in vivo. These results suggest that vascular endothelium can act as an APC for CD8+ direct allorecognition and may, therefore, play an important role in regulating immune processes of allograft rejection.




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