1. Leishmania major induces differential expression of costimulatory molecules on mouse epidermal cells.
- Author
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Mbow ML, DeKrey GK, and Titus RG
- Subjects
- Animals, Antibodies, Monoclonal, CD40 Antigens metabolism, Cell Line, Disease Susceptibility, Down-Regulation, Enzyme-Linked Immunosorbent Assay, Epidermal Cells, Flow Cytometry, Interferon-gamma metabolism, Interleukin-4 metabolism, Keratinocytes metabolism, Langerhans Cells metabolism, Mice, Mice, Congenic, Mice, Inbred BALB C, Mice, Inbred C3H, Models, Animal, Signal Transduction, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Helper-Inducer metabolism, Up-Regulation, B7-1 Antigen metabolism, Epidermis metabolism, Leishmania major immunology
- Abstract
Levels of expression of costimulatory molecules have been proposed to influence the outcome of antigen-specific T cell priming. We found that Leishmania major selectively modulated the expression of costimulatory molecules on various populations of epidermal cells. B7.2 expression was down-regulated on Thy1.2+ epidermal cells (keratinocytes) from disease-resistant C3H mice, but not from disease-susceptible BALB/c mice. In addition, epidermal cells from BALB/c mice showed a down-regulation of B7.1 expression on NLDC 145+ Langerhans cells. In vitro T cell priming experiments, using syngeneic epidermal cells as antigen-presenting cells (APC), showed that the production of IFN-gamma was inhibited when either B7.1 or B7.2 signaling pathways were blocked. Blockade of B7.2, but not B7.1, significantly inhibited the ability of epidermal cells to induce IL-4 production from CD4+ T cells. In addition, C3H CD4+ T cells, which were unable to secrete detectable levels of IL-4 in cultures with syngeneic APC, were now able to secrete IL-4 following presentation of L. major antigens by congenic BALB/K epidermal cells. Conversely, C3H epidermal cells supported the priming of BALB/K CD4+ T cells for IL-4 production in vitro. Thus, the differential expression of B7 molecules on epidermal cells may not represent the sole factor governing the polarization of L. major-specific CD4+ T cells in vitro.
- Published
- 2001
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