Mouse vascular endothelium activates CD8+ T lymphocytes in a B7-dependent fashion.
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-2(b)) vascular endothelial cells as stimulators and CD8(+) T lymphocytes isolated from CBA/J (H-2(k)) 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 CD44(low) 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-x(L). Treatment with CTLA4-Ig led to marked reduction of T cell proliferation and a decrease in expression of Bcl-x(L). 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.
Kreisel
Daniel
D
Department of Surgery, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Krupnick
Alexander S
AS
Balsara
Keki R
KR
Riha
Markus
M
Gelman
Andrew E
AE
Popma
Sicco H
SH
Szeto
Wilson Y
WY
Turka
Laurence A
LA
Rosengard
Bruce R
BR
D000069594:Abatacept; D000818:Animals; D017951:Antigen Presentation; D017209:Apoptosis; D018122:B7-1 Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D018796:Immunoconjugates / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014184:Transplantation, Homologous; D051020:bcl-X Protein
D018122:B7-1 Antigen; C494812:Bcl2l1 protein, mouse; D015395:Histocompatibility Antigens Class I; D018796:Immunoconjugates; D007376:Interleukin-2; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D000069594:Abatacept; D007371:Interferon-gamma