The Role of Fibroblasts in Thymocyte-Positive Selection

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 mi...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-11, Vol.169 (9), p.4945-4950
Main Authors: Lilic, Mirjana, Santori, Fabio R, Neilson, Eric G, Frey, Alan B, Vukmanovic, Stanislav
Format: Article
Language:English
Subjects:
Animals
ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters - biosynthesis
ATP-Binding Cassette Transporters - genetics
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
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Description
Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.169.9.4945