Immune tolerance through mixed hematopoietic chimerism

• Main Authors: Jeng Chang Chen, 陳正昌
• Other Authors: M. L. Kuo
• Format: Others
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/59442755679554731630

博士 === 長庚大學 === 臨床醫學研究所 === 99 === The presence of tolerance in a state of hematopoietic chimerism remains a matter of debate. Using an allogeneic murine model of in utero marrow transplantation, I created hematopoietic chimerism to elucidate the immunological significance of chimerism towards tolerance. Chimerism rate and level exhibited a dose response to marrow transplants, in which T cells could facilitate engraftment at the expense of graft-versus-host disease as observed in postnatal marrow transplantation. Tolerance didn’t relate to marrow doses but rather ultimate peripheral chimerism achieved. Peripheral chimerism linearly related to thymic chimerism, and predicted the degree of graft acceptance with levels >3% at skin placement yielding consistent skin tolerance. The loss of peripheral chimerism caused the failure of accepting donor skin except for prior donor skin acceptance at sufficient chimerism levels. It suggests an immunomodulatory effect of chimerism on donor-specific immunosuppression to facilitate the establishment of complete skin tolerance. However, it couldn’t be potentiated by postnatal donor lymphocyte infusion despite a transient uprise of chimerism levels. There is immunological memory of skin tolerance that didn’t relate to whether chimerism could be detected anywhere in the recipients and alloantigens on accepted skins, nor solely the effects of regulatory T cells or clonal anergy. It’s concluded that hematopoietic chimerism was immunologically relevant to induction of skin tolerance but not to its maintenance.