Corneal endothelial cells inhibit T cell proliferation by blocking IL-2 production.
We have reported that Ia+ LEW rat corneal endothelial (CE) cells could not induce Ag-specific proliferation of MHC compatible T cell lines. Instead, the presence of CE cell monolayers inhibited T cell proliferation assays. We now report on the effect of CE cells on IL-2 production, IL-2R expression, and IL-2 responsiveness of T cells. Ag-specific growth inhibition of the 1C3.4 T cell hybridoma was unaffected by the presence of CE cells but IL-2 production was suppressed by CE cells. Similar CE cell-mediated inhibition of IL-2 secretion was found with fresh splenic lymphocytes stimulated by Con A. Controls showed that neither CE cells nor their supernatant affected the CTLL cell response to rIL-2, allowing reliable measurement of IL-2 production. Further evidence that the block is at the level of IL-2 production was shown by the observation that IL-2R expression was up-regulated after TCR occupancy whether or not CE cells were present. Also, T cells expressing IL-2R were responsive to exogenous rIL-2 whether or not CE cells were present. CE cells themselves do not induce IL-2R expression or IL-2 responsiveness. Under normal culture conditions, the R1170 rat T cell line continually expresses a significant level of IL-2R and dies before IL-2R is down-regulated to background levels. However, in the presence of CE cells, these R1170 cells down-regulate IL-2R and lose IL-2 responsiveness while remaining viable.
Kawashima
H
H
Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
Prasad
S A
SA
Gregerson
D S
DS
D000818:Animals; D002478:Cells, Cultured; D003315:Cornea / Q000276:immunology*; D015536:Down-Regulation; D004727:Endothelium / Q000276:immunology; D005260:Female; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D008213:Lymphocyte Activation; D051381:Rats; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology; D015854:Up-Regulation
D007376:Interleukin-2; D015375:Receptors, Interleukin-2