Local regulation of immune responses: corneal endothelial cells alter t cell activation and cytokine production.
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 ([Ca(2+)](i)) increase induced by TCR ligation, but not the [Ca(2+)](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 beta (TGF-beta) and may contribute to local immune privilege.
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Department of Microbiology, University of Minnesota, Minneapolis, MN, USA.
Gregerson
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Kawashima
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D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D003315:Cornea / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors; D004727:Endothelium / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D015847:Interleukin-4 / Q000037:antagonists & inhibitors; D015848:Interleukin-5 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D016207:Cytokines; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D015847:Interleukin-4; D002118:Calcium