International Immunology, Vol. 12, No. 6, 937-948,
June 2000
© 2000 Japanese Society for Immunology
Th1 transmigration anergy: a new concept of endothelial cell–T cell regulatory interaction
1 Department of Immunology, The Forsyth Institute, 140 Fenway, Boston, MA 02115, USA
2 Mitsubishi-Tokyo Pharmaceuticals, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227, Japan
3 Department of Periodontology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku,Tokyo 113, Japan
Correspondence to: M. A. Taubman
Stimulation of endothelial cells (EC) with IFN-
generates selective enhancement of Th1 cell transmigration and induction of MHC class II expression on EC. In the present study, we tested whether antigen presentation by EC could influence transmigrating T cells in an in vitro system. Bacterial antigen presentation by EC from primary culture and after cloning induced antigen-specific anergy of transmigrating Th1 clone cells in a MHC class II-dependent manner as characterized by non-responsiveness to subsequent antigen presentation and inability to produce IL-2. This T cell transmigration anergy induced by EC was abrogated by anti-rat CD28 mAb, suggesting that lack of B7 co-stimulatory signals by EC might be related to the induction of anergy. While MHC class II expression on primary and cloned EC was observed after IFN- stimulation, these cells never expressed B7. B7-1 gene-transfected endothelial clone cells
(ECC/B7-1) were developed to elucidate the influence of B7 co-stimulation by EC. ECC/B7-1 induced proliferation of Th1 clone cells, whereas ECC did not induce proliferation in co-culture of Th1 clone cells and EC stimulated with IFN- and antigen. In the transmigration assay, ECC/B7-1 did not induce transmigration anergy of Th1 clones or Th1 lines unless anti-rat B7-1 blocking mAb was added. Therefore, in rats, the T cell anergy induced during transmigration across a layer of EC seemed to be due to antigen presentation in the absence of B7 on the EC. We introduce the concept of transmigration anergy in this manuscript. Thus, EC can play a critical immune regulatory role in the context of antigen presentation by MHC class II to transmigrating T cells.
Keywords: anergy, B7, MHC class II, T cell migration, vascular endothelium
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