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Embryonic Stem Cells |
1 Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, 91904 Jerusalem, Israel
2 Department of Immunology, Weizmann Institute of Science, 76100 Rehovot, Israel
3 The Lautenberg Center for General and Tumor Immunology, Hadassah Medical School, The Hebrew University, 91120 Jerusalem, Israel
* To whom correspondence should be addressed. E-mail: dmicha{at}stanford.edu.
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Abstract |
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Differentiated cell types derived from human embryonic stem cells (HESCs) may serve in the future to treat various human diseases. A crucial step towards their successful clinical application is to examine the immune response that might be launched against them following transplantation. We used two experimental platforms to examine the in vivo leukocyte response towards HESCs: i) immunocompetent and immunodeficient mouse strains were used to identify T cells as the major component that cause xenorejection of HESCs. ii) Mice that were conditioned to carry peripheral blood leukocytes from human origin were used to test the human leukocyte alloresponse towards undifferentiated and differentiated HESCs. Utilizing this model we have detected only a minute immune response toward undifferentiated as well as differentiated HESCs over the course of one month, although control adult grafts were repeatedly infiltrated with lymphocytes and destroyed. Our data shows that the cells evade immune destruction due to a low immunostimulatory potential. Nevertheless, a human cytotoxic T lymphocyte clone that was specifically prepared to recognize two HESC lines could lyse the cells following MHC-I induction. Although MHC-I levels in HESCs are sufficient for rejection by cytotoxic T cells, our data suggests that the immunostimulatory capacity of the cells is very low. Thus, immunosuppressive regimes for HESC based therapeutics could be highly reduced in comparison to conventional organ transplantation since direct allorejection processes of HESCs and their derivatives are considerably weaker.
Key Words. Human embryonic stem cells (HESCs), Peripheral blood mononuclear cells (PBMCs), Embryoid bodies (EBs), Cytotoxic T lymphocytes (CTLS)
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