Murine keratocytes function as antigen-presenting cells

Area of Science:

• Immunology
• Ophthalmology
• Cell Biology

Background:

• Keratocytes constitutively express MHC class I and costimulatory molecules like B7-1 and ICAM-1.
• IFN-gamma stimulation induces MHC class II expression on keratocytes.
• These molecules suggest keratocytes can present antigens and provide costimulatory signals to T cells.

Purpose of the Study:

• To investigate the antigen-presenting and costimulatory capabilities of mouse corneal keratocytes.
• To determine if keratocytes can activate T cells in an antigen-specific manner.
• To explore the role of keratocytes in immune-mediated corneal inflammation.

Main Methods:

• Incubation of mouse T cells (CD4+ and CD8+) with irradiated keratocytes.
• Use of anti-CD3 mAb and anti-B7-1 mAb to assess T cell proliferation and costimulation.
• Incubation of T cells from herpes-infected mice with HSV-1-infected keratocytes to evaluate antigen-specific activation.
• Measurement of T cell proliferation and Th1 cytokine production (IL-2, IFN-gamma).

Main Results:

• Keratocytes expressing B7-1 provided a costimulatory signal to both CD4+ and CD8+ T cells, enhancing their proliferation.
• This costimulatory effect was inhibited by anti-B7-1 mAb.
• HSV-1-infected keratocytes activated T cells from herpes-infected mice, leading to proliferation and Th1 cytokine production.
• Keratocytes presented viral antigens, demonstrating antigen-specific T cell activation.

Conclusions:

• Mouse corneal keratocytes function as potent antigen-presenting cells.
• Keratocytes provide both antigen-specific and costimulatory signals essential for T cell activation.
• These findings highlight the role of keratocytes in initiating and modulating immune responses within the corneal stroma.
• Keratocytes may contribute to immune-mediated stromal keratitis, including herpetic stromal keratitis.