A thymic epithelial cell line induces both positive and negative selection in the thymus.
TCR engagement in the thymus results in both survival and elimination signals for developing thymocytes. To examine whether both signals can be provided by the same cell type, we investigated the ability of a thymic epithelial cell (TEC) line 427.1, previously shown to allow positive selection in the thymus, to induce clonal deletion of immature thymocytes. [H-2b/s-->H-2s] bone marrow chimeras are non-responsive to antigens in the context of H-2b. However, chimeras that underwent intrathymic injection of H-2b/s 427.1 cells expressing vesicular stomatitis virus (VSV) nucleocapsid antigen acquired the ability to raise influenza, but not VSV specific H-2b restricted cytotoxic T lymphocyte (CTL) responses. The ability of 427.1 cells to delete CD4+CD8+ thymocytes was determined using mice transgenic for the TCR specific for ovalbumin (OVA) in the context of H-2Kb. OVA transfected, but not mock transfected 427.1 TECs, induced in vitro deletion of CD4+CD8+ TCR transgenic thymocytes manifested as a down-modulation of CD4 and CD8 molecules, a shift in the side versus forward scatter characteristics of thymocytes, and appearance of thymocytes with subdiploid content of DNA indicated the ongoing process of DNA fragmentation. The finding that the same TEC line is capable of inducing both positive and negative selection in the thymus suggests that thymocytes bearing TCRs specific for self peptides expressed by positively selecting thymic epithelium can be deleted. Therefore the expression of a unique set of MHC associated peptides by TECs does not appear to be the basis for the positive outcome of the TCR ligation on immature thymocytes.
Vukmanović
S
S
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle 98195.
Jameson
S C
SC
Bevan
M J
MJ
D000818:Animals; D002460:Cell Line; D002678:Chimera; D004847:Epithelial Cells; D005434:Flow Cytometry; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology*; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin