Human endothelial cell costimulation of T cell IFN-gamma production.
In this report, we show that human endothelial cells (EC) provide costimulatory signals to mitogen-activated CD4+ T cells to augment IFN-gamma production. We also show that EC can enhance responsiveness of the T cells to IL-12. While IL-12 has no effect on IFN-gamma production by cultured CD4+ T cells in the absence of EC, addition of IL-12 to T cell-EC cocultures augments IFN-gamma production by as much as fivefold. Separation of T cells from EC by a semipermeable membrane inhibits the effect of EC and IL-12 on IFN-gamma production. Anti-LFA-3 Abs, in the absence or presence of IL-12, inhibit EC costimulation of IFN-gamma production by up to 50%, while Abs to intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), LFA-1, and very late antigen-4 (VLA-4) have relatively little effect. Pretreatment of T cells with conditioned medium from T cell-EC cocultures, or with IL-2 or IL-1 alpha similarly primes CD4+ T cells for the costimulatory effect of IL-12 on IFN-gamma production. EC costimulation of IFN-gamma production is inhibited by cyclosporine. However, in the presence of IL-12 there is a marked resistance to this inhibitory effect, suggesting that the IL-12-induced costimulatory pathway is distinct from the costimulatory pathway activated by endothelium alone. Our data are consistent with the hypothesis that, as a consequence of interactions with endothelium, T cells that migrate into an inflammatory site are primed to have enhanced responses to Ag and cytokine(s), such as IL-12, that influence T cell-cytokine production.
Briscoe
D M
DM
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Henault
L E
LE
Geehan
C
C
Alexander
S I
SI
Lichtman
A H
AH
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects; D018664:Interleukin-12 / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects
D016207:Cytokines; D018664:Interleukin-12; D007371:Interferon-gamma; D016572:Cyclosporine