Corneal endothelial cells (CE cells) inhibit antigen- and mitogen-activated lymphocyte proliferation assays, although interleukin 2 receptor (IL-2R) expression and responsiveness to exogenous IL-2 are unaffected. To examine this activity further, co-cultures of CE cells and T cell clones were studied. CE cells inhibited IL-2 and IL-4 production by T cells stimulated with Ag and APC, but not IL-5 or IL-6 production. CE cells also inhibited NFAT-driven lacZ reporter gene production following Ag stimulation of transfected KZO T hybridoma cells. Conversely, stimulation of IL-2 production by ionomycin, with or without PMA, was unaffected by the CE cells. Preincubation of KZO hybridoma or Jurkat cells with CE cells, or CE cell-conditioned culture supernatant, inhibited the intracellular calcium ([Ca2+](i)) increase induced by TCR ligation, but not the [Ca2+](i) increase induced by ionomycin or thapsigargin. The inhibitory effect was independent of APC and did not act by blocking costimulation, since IL-2 production stimulated by immobilized anti-CD3 alone was also inhibited by CE cells. The supernatant factor was heat labile. This novel activity is unlike other immunoregulatory molecules, including transforming growth factor β (TGF-β) and may contribute to local immune privilege. (C) 2000 Academic Press.
Bibliographical noteFunding Information:
We thank Drs Steve Jameson and Susan Kierstad for advice on the Ca2+ studies and Janet Peller for assistance with flow cytometry. This work was supported by NIH grant EY09207, Research to Prevent Blindness, Inc., the Minnesota Lions and Lionesses Clubs, and the Anna Heilmaier Fund.
- Cellular activation
- Signal transduction
- T lymphocytes