Abstract
Despite significant progress in the past 20 years, induction of tolerance to host and donor HLA antigens after allogeneic transplantation, remains a rare event. Graft rejection and graft-versus-host disease (GVHD) are still the major obstacles to reach long-term engraftment and disease-free survival in patients transplanted with allogeneic hematopoietic stem cells, or solid organs.1,2 Allograft rejection and GVHD are mainly due to activation of alloreactive T cells of host and donor origin, respectively. The recognition of alloantigens presented by either allogeneic, or autologous antigen-presenting cells (APC) results in activation of these allogeneic T cells.3 This initial immune response leads to a cascade of events, including up-regulation of adhesion molecules, activation of macrophages, migration of T cells and recruitment of other effector. cells, which cause tissue damage and the appearance of clinical manifestations of graft rejection and GVHD.4,5 A large body of evidence supports the notion that cytokines play a critical role in these events. In particular, IL-2 and IFN-γ produced by the alloreactive T cells are involved in the initial amplification of the allogeneic responses, whereas IL-1 and TNF-α, produced by the APC, significantly contribute to the strong inflammatory responses which are characteristic for these diseases.5–7Therefore, modulation of cytokine production may represent a valuable target for immunosuppression.
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Roncarolo, MG. (1995). Interleukin-10 and Transplantation Tolerance. In: Interleukin-10. Molecular Biology Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-22038-2_12
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DOI: https://doi.org/10.1007/978-3-662-22038-2_12
Publisher Name: Springer, Berlin, Heidelberg
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