TY - JOUR
T1 - Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells
AU - Drukker, Micha
AU - Katchman, Helena
AU - Katz, Gil
AU - Friedman, Smadar Even Tov
AU - Shezen, Elias
AU - Hornstein, Eran
AU - Mandelboim, Ofer
AU - Reisner, Yair
AU - Benvenisty, Nissim
PY - 2006/2
Y1 - 2006/2
N2 - Differentiated cell types derived from human embryonic stem cells (hESCs) may serve in the future to treat various human diseases. A crucial step toward their successful clinical application is to examine the immune response that might be launched against them after transplantation. We used two experimental platforms to examine the in vivo leukocyte response toward hESCs. First, immunocompetent and immunodeficient mouse strains were used to identify T cells as the major component that causes xenorejection of hESCs. Second, mice that were conditioned to carry peripheral blood leukocytes from human origin were used to test the human leukocyte alloresponse toward undifferentiated and differentiated hESCs. Using this model, we have detected only a minute immune response toward undifferentiated as well as differentiated hESCs over the course of 1 month, although control adult grafts were repeatedly infiltrated with lymphocytes and destroyed. Our data show 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 after major histocompatibility complex class I (MHC-I) induction. Although MHC-I levels in hESCs are sufficient for rejection by cytotoxic T cells, our data suggest that the immunostimulatory capacity of the cells is very low. Thus, immunosuppressive regimens for hESC-based therapeutics could be highly reduced compared with conventional organ transplantation because direct allorejection processes of hESCs and their derivatives are considerably weaker.
AB - Differentiated cell types derived from human embryonic stem cells (hESCs) may serve in the future to treat various human diseases. A crucial step toward their successful clinical application is to examine the immune response that might be launched against them after transplantation. We used two experimental platforms to examine the in vivo leukocyte response toward hESCs. First, immunocompetent and immunodeficient mouse strains were used to identify T cells as the major component that causes xenorejection of hESCs. Second, mice that were conditioned to carry peripheral blood leukocytes from human origin were used to test the human leukocyte alloresponse toward undifferentiated and differentiated hESCs. Using this model, we have detected only a minute immune response toward undifferentiated as well as differentiated hESCs over the course of 1 month, although control adult grafts were repeatedly infiltrated with lymphocytes and destroyed. Our data show 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 after major histocompatibility complex class I (MHC-I) induction. Although MHC-I levels in hESCs are sufficient for rejection by cytotoxic T cells, our data suggest that the immunostimulatory capacity of the cells is very low. Thus, immunosuppressive regimens for hESC-based therapeutics could be highly reduced compared with conventional organ transplantation because direct allorejection processes of hESCs and their derivatives are considerably weaker.
KW - Cytotoxic T lymphocytes
KW - Embryoid bodies
KW - Human embryonic stem cells
KW - Peripheral blood mononuclear cells
UR - http://www.scopus.com/inward/record.url?scp=33646692132&partnerID=8YFLogxK
U2 - 10.1634/stemcells.2005-0188
DO - 10.1634/stemcells.2005-0188
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C2 - 16109762
AN - SCOPUS:33646692132
SN - 1066-5099
VL - 24
SP - 221
EP - 229
JO - Stem Cells
JF - Stem Cells
IS - 2
ER -