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Effect of human corneal fibroblasts on lymphocyte proliferation in vitro
J J Donnelly1, L S Chan, M S Xi
1Department of Ophthalmology, Scheie Eye Institute, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Abstract:
Cocultivation of human corneal fibroblasts (CFB) with allogeneic peripheral blood mononuclear cells (PBL) induced a minimal lymphocyte proliferative response, even when the fibroblasts had been pre-treated with interferon-gamma (IFN-gamma) and were HLA-DR positive. IFN-gamma-treated CFB did not express detectable HLA-DQ alloantigens. Cocultivation of CFB with PBL in the presence of Concanavalin A (Con A) or Phytohemagglutinin inhibited mitogen-induced lymphocyte proliferation by 40-90% relative to PBL cultured without CFB. Induction of HLA-DR expression on the CFB did not alter their inhibitory properties. Addition of indomethacin to cultures reversed the effect of CFB on Con A responses. However, no difference between proliferative responses to HLA-DR positive or negative CFB was seen in the presence of indomethacin. This weak response to induced Class II alloantigens on CFB suggests that induction of Class II alloantigens on corneal stroma alone may be insufficient to sensitize a recipient for Class II alloantigen-driven corneal graft rejection.
Insights
Human corneal fibroblasts (CFB) minimally stimulated lymphocytes, even when treated with interferon-gamma (IFN-gamma). CFB inhibited mitogen-induced proliferation, suggesting corneal alloantigens alone may not cause graft rejection.
Area of Science:
- Immunology
- Ophthalmology
- Transplantation immunology
Background:
- Corneal graft rejection is a significant clinical challenge.
- Understanding the immunogenicity of corneal tissue is crucial for improving graft survival.
- Class II alloantigens on corneal cells may play a role in immune responses.
Purpose of the Study:
- To investigate the immunogenicity of human corneal fibroblasts (CFB) in vitro.
- To determine if inducing Class II alloantigens on CFB can elicit a lymphocyte response.
- To assess the role of CFB in modulating immune cell proliferation.
Main Methods:
- Cocultivation of CFB with peripheral blood mononuclear cells (PBL).
- Treatment of CFB with interferon-gamma (IFN-gamma) to induce HLA-DR and HLA-DQ expression.
- Assessment of lymphocyte proliferation in response to CFB using mitogens (Concanavalin A, Phytohemagglutinin).
- Inhibition studies with indomethacin.
Main Results:
- CFB induced minimal lymphocyte proliferation, even when expressing HLA-DR.
- IFN-gamma-treated CFB did not express detectable HLA-DQ.
- CFB significantly inhibited mitogen-induced lymphocyte proliferation (40-90%).
- Indomethacin reversed the inhibitory effect of CFB on lymphocyte proliferation.
- No difference in proliferation was observed between HLA-DR positive and negative CFB in the presence of indomethacin.
Conclusions:
- Induction of Class II alloantigens on corneal fibroblasts alone is insufficient to elicit a strong allogeneic T-cell response.
- Corneal fibroblasts possess inhibitory properties that can suppress lymphocyte proliferation.
- These findings suggest that corneal alloantigens may not be the primary drivers of Class II alloantigen-mediated corneal graft rejection.