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Antigen presenting function of class II MHC expressing pancreatic beta cells
J Markmann1, D Lo, A Naji
1Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia 19104.
Nature
|December 1, 1988
Summary
Transgenic pancreatic islet cells expressing foreign class II MHC molecules did not elicit immune rejection. Instead, these non-lymphoid cells induced antigen-specific unresponsiveness, suggesting a role in maintaining self-tolerance.
Area of Science:
- Immunology
- Transplantation Biology
- Cellular Immunology
Background:
- Class II Major Histocompatibility Complex (MHC) gene expression is typically restricted to immune cells like B lymphocytes and macrophages/dendritic cells.
- These Class II-bearing cells function as antigen-presenting cells (APCs), crucial for T lymphocyte activation.
- The role of non-immune cells expressing Class II MHC in immune responses and tolerance is not fully understood.
Purpose of the Study:
- To investigate whether non-bone-marrow-derived cells, specifically pancreatic islet beta cells, can acquire antigen-presenting cell (APC) function through the expression of foreign Class II (I-E) molecules.
- To determine if transgenic expression of Class II MHC on islet cells can elicit graft rejection or induce immune tolerance.
- To explore the potential extrathymic mechanisms for maintaining self-tolerance.
Main Methods:
- Generation of transgenic mice with pancreatic islet beta cells expressing a foreign Class II (I-E) molecule.
- In vivo studies involving transplantation of I-E positive (I-E+) transgenic islets into I-E negative (I-E-) host mice.
- In vitro assays to assess the ability of I-E+ beta cells to stimulate T lymphocytes in the presence of antigen.
Main Results:
- Grafts of I-E+ transgenic islets were not rejected in naive I-E- hosts unless the host was primed with I-E+ spleen cells.
- In vitro, I-E+ beta cells failed to stimulate T lymphocytes reactive to I-E plus a peptide antigen.
- Paradoxically, the I-E+ beta cells induced antigen-specific unresponsiveness in T cells.
Conclusions:
- Expression of Class II MHC molecules on non-lymphoid cells, such as pancreatic islet beta cells, does not necessarily lead to immune rejection.
- These non-immune cells expressing Class II MHC can induce antigen-specific T cell unresponsiveness, a key feature of immune tolerance.
- This suggests a potential extrathymic role for non-lymphoid Class II MHC expression in maintaining self-tolerance, complementing thymic education.