Leishmania major induces differential expression of costimulatory molecules on mouse epidermal cells.
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.
Mbow
M L
ML
Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523-1671, USA.
DeKrey
G K
GK
Titus
R G
RG
D000818:Animals; D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D002460:Cell Line; D004198:Disease Susceptibility; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D023421:Models, Animal; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D019013:CD40 Antigens; D015847:Interleukin-4; D007371:Interferon-gamma