Fibroblasts can Induce Thymocyte Positive Selection in vivo

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 21; pp. 10335 - 10339
• Main Authors: Hugo, Patrice, Kappler, John W., McCormack, James E., Marrack, Philippa
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.11.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antigens; Biological and medical sciences; Cell Line; Cell lines; Cellular biology; Chimera; Chimeras; Epithelial cells; Fetus; Fibroblasts; Fibroblasts - physiology; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; H-2 Antigens - immunology; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - immunology; Histocompatibility Antigens Class II - metabolism; Immunity (Disease); Immunobiology; Liver cells; Lymphocyte Activation; Major Histocompatibility Complex; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Molecules; Organs and cells involved in the immune response; Positive selection; T lymphocytes; T-Lymphocytes - immunology; Thymocytes; Transfection; Antigen presentation; Thymus gland; Thymocyte; Major histocompatibility system; Selection; Rodentia; Class II histocompatibility antigen; Molecular interaction; Cell differentiation; Vertebrata; Mammalia; Lymphoid organ; Mouse; Fibroblast; Chimera
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.21.10335

During development in the thymus, thymocytes bearing αβ T-cell receptors are selected to mature if the receptors they bear are able to interact in some way with major histocompatibility complex (MHC) proteins expressed on thymic stromal cells. It has been shown that thymus cortical epithelial cells are usually the cells presenting the MHC molecules involved in this process of so-called positive selection. Here we tested the ability of fibroblasts to mediate positive selection in vivo. Fibroblasts transfected with the genes for the MHC I-Abproteins were injected intrathymically into irradiated H-2kanimals reconstituted with H-2bxkF1fetal liver cells. Eight weeks later, the recipient mice were immunized and shown to contain peptide-specific I-Ab-restricted T cells. This demonstrates the ability of I-Ab-transfected fibroblasts to participate in positive selection. Thus a cell type that is not specialized to process and present antigens in the context of MHC class II molecules can mediate positive selection when transfected with an appropriate MHC molecule. The data also support the idea that the ability to mediate positive selection may not be limited to thymic cortical epithelium.