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Tolerance and immunity following in utero transplantation of allogeneic fetal liver cells: the cytokine shift

Sefrioui H, Donahue J, Gilpin EA, Srivastava AS, Carrier E. Cell Transplant. 2003;12(1):75-82.

Abstract

Although in utero transplantation (IUT) has resulted in donor-specific tolerance to posnatal solid organ transplantation, the mechanisms of this tolerance remain poorly understood. Our recent findings demonstrate that under specific conditions prenatal injection of allogeneic cells may lead to allosensitization instead of tolerance. The present study explored the role of CD4 cells, cytokines, and I-E superantigen in developing tolerance vs. immunity after in utero transplantation. Sixteen animals survived IUT (40-60% survival rate) and were free from any signs of graft-versus-host disease (GVHD).The TH1 –> TH2 shift was associated with tolerance and TH2 –> TH1 shift with allosensitization. Our results showed that tolerant BALB/c (H-2d, I-E+) –> CS7BL/6 (H-2b, I-E-) (2/7) mice showed higher IL-4 (p < 0.05) in antidonor MLR, and partial deletion of recipient I-E-reactive T cells (CD3Vbeta11) (p < 0.045). On the other hand, nontolerant animals (5/7) demonstrated high production of IFN-gamma (p < 0.05) without deletion of CD3Vbeta11 T cells.

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