The role of fibroblasts in thymocyte-positive selection

J Immunol. 2002 Nov 1;169(9):4945-50. doi: 10.4049/jimmunol.169.9.4945.

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