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The Role of Fibroblasts in Thymocyte-Positive Selection¹

Mirjana Lili^*, Fabio R. Santori^*, Eric G. Neilson, Alan B. Frey and Stanislav Vukmanovi^2,*

Department of ^* Pathology, Michael Heidelberger Division of Immunology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY 10016; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232; and Department of Cell Biology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY 10016

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-. Positive selection of CD4^-CD8⁺ thymocytes was observed in neither adult nor fetal/neonatal thymus of transgenic mice. IFN--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.

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