IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells

✍ Scribed by Christian A. Gleissner; Arne Zastrow; Roland Klingenberg; Martin S. Kluger; Mathias Konstandin; Sultan Celik; Susanne Haemmerling; Vijay Shankar; Thomas Giese; Hugo A. Katus; Thomas J. Dengler

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 628 KB
• Volume: 37
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200636498

✦ Synopsis

Abstract

Effects of IL‐10 on endothelium‐dependent T cell activation have not been investigated in detail. We confirm expression of the IL‐10 receptor and effective signaling via STAT‐3 in human umbilical vein endothelial cells (HUVEC). In CD4 T cell cocultures with HUVEC, pretreatment of endothelial cells with IL‐10 resulted in significant dose‐dependent inhibition of CD4 T cell proliferation, which also occurred when IL‐10 was removed after pretreatment before starting cocultures. Th1/Th2 polarization of proliferated T cells, endothelial nitric oxide (NO), or IL‐12 production were unchanged. However, IL‐10 stimulation resulted in up‐regulation of SOCS‐3, a negative regulator of cytokine secretion, and induction of the inhibitory surface molecules immunoglobulin‐like transcript 3 and 4 (ILT3/ILT4) in EC, potentially involving glucocorticoid‐induced leucine zipper (GILZ). Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation. In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation. No induction of foxp3^+^ regulatory T cells was seen. In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL‐10 due to up‐regulation of ILT3/ILT4, obviously not involving generation of Treg. This identifies a novel action of IL‐10 in EC and a potential therapeutical target for local immunomodulation.