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Published on: July 28, 2010
Leishmania major induces differential expression of costimulatory molecules on mouse epidermal cells
M L Mbow1, G K DeKrey, R G Titus
1Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523-1671, USA.
Insights
Leishmania major infection alters costimulatory molecule expression on skin cells, impacting T cell responses. Differential B7 molecule expression on epidermal cells influences T helper cell polarization during Leishmania major infection.
Area of Science:
- Immunology
- Dermatology
- Parasitology
Background:
- Costimulatory molecules are crucial for T cell priming and immune response outcomes.
- Leishmania major infection is known to modulate immune cell function in the skin.
Purpose of the Study:
- To investigate how Leishmania major infection affects the expression of costimulatory molecules on epidermal cells.
- To determine the role of these modulated costimulatory molecules in T cell polarization during Leishmania major infection.
Main Methods:
- Analysis of B7.1 and B7.2 expression on epidermal cells (keratinocytes and Langerhans cells) from resistant (C3H) and susceptible (BALB/c) mice infected with Leishmania major.
- In vitro T cell priming experiments using antigen-presenting cells (APCs) from these mice, with blockade of B7.1 or B7.2 signaling pathways.
- Assessment of cytokine production (IFN-gamma and IL-4) by CD4+ T cells.
Main Results:
- Leishmania major down-regulated B7.2 on keratinocytes in resistant mice and B7.1 on Langerhans cells in susceptible mice.
- Blocking B7.1 or B7.2 signaling inhibited IFN-gamma production.
- Blocking B7.2 significantly inhibited IL-4 production by CD4+ T cells.
- Differential expression of B7 molecules on epidermal cells influenced IL-4 secretion by CD4+ T cells in a strain-dependent manner.
Conclusions:
- Leishmania major selectively modulates B7.1 and B7.2 expression on epidermal cells in a mouse strain-dependent manner.
- These differential expression patterns impact T cell polarization, specifically IL-4 production.
- The findings suggest that epidermal B7 molecule expression is a key factor, but not the sole determinant, in governing Leishmania major-specific CD4+ T cell responses.
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.
