Abstract
Mice with fibroblast-specific expression of TAP-1 were generated by expressing the TAP-1 transgene under the control of the fibroblast-specific protein (FSP) 1 promoter/enhancer on TAP-1-deficient background. MHC class I expression in primary fibroblast cultures isolated from the resulting strain mimicked that of wild-type counterparts. MHC class I was detected in both types of fibroblasts following treatment with IFN-alphabeta. Positive selection of CD4(-)CD8(+) thymocytes was observed in neither adult nor fetal/neonatal thymus of transgenic mice. IFN-alphabeta-induced expression of MHC class I rescued positive selection of CD4(-)CD8(+) T cells in fetal thymic organ cultures, but not in adult mice. Contrary to previous suggestions, our results indicate a limited role of fibroblasts in promoting positive selection. In addition, the results suggest that positive selection may occur by a different mechanism in fetal vs adult thymus.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP-Binding Cassette Transporters / biosynthesis
-
ATP-Binding Cassette Transporters / genetics
-
Animals
-
CD4-Positive T-Lymphocytes / cytology
-
CD4-Positive T-Lymphocytes / immunology
-
CD4-Positive T-Lymphocytes / metabolism
-
CD8-Positive T-Lymphocytes / cytology
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Differentiation / immunology
-
Cells, Cultured
-
Fetus
-
Fibroblasts / cytology*
-
Fibroblasts / immunology*
-
Fibroblasts / metabolism
-
Gene Expression / immunology
-
Histocompatibility Antigens Class I / biosynthesis
-
Humans
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Organ Culture Techniques
-
T-Lymphocyte Subsets / cytology*
-
T-Lymphocyte Subsets / immunology*
-
T-Lymphocyte Subsets / metabolism
-
Thymus Gland / cytology*
-
Thymus Gland / immunology*
-
Thymus Gland / metabolism
-
Transgenes / immunology
-
Up-Regulation / immunology
Substances
-
ATP Binding Cassette Transporter, Subfamily B, Member 2
-
ATP-Binding Cassette Transporters
-
Histocompatibility Antigens Class I
-
TAP1 protein, human
-
Tap1 protein, mouse