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Microchimerism and the importance of semi-allogeneic donor-derived bone marrow cells in graft survival.

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Author(s):
Luciana de Deus Vieira de Moraes
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Luiz Vicente Rizzo; Magnus Ake Gidlund; Luiza Guilherme Guglielmi; Maria Gerbase de Lima; Jose Osmar Medina de Abreu Pestana
Advisor: Luiz Vicente Rizzo
Abstract

Tolerance induction to allografts by the administration of donor cells before transplantation has been shown to be efficient, even in non immunosuppressed hosts. There are conflicting reports in the literature regarding the role of microchimerism and tolerance to alloantigens. In the present work, augmentation of skin and cardiac survival time was observed after the infusion of a mixture of donor (BALB/c x C57BI/6)F1 spleen and bone marrow cells twenty-one days before transplantation, specially when compared to donor spleen cell receptors. The establishment of microchimerism, correlation with graft survival time and possible mechanisms involved in this strategy were investigated. An overproduction of IL-10 in the supernatants from spleen cell cultures of mice inoculated with semi-allogeneic cells was observed. Mice that received donor spleen cells only showed increased number of B lymphocytes. Moreover, the establishment of microchimerism did not correlate to tolerance to cardiac allografts despite the augmentation of graft survival time. These results suggest that the development of microchimerism does not prevent graft rejection and that there is a role for IL-10 in graft survival when donor spleen and bone marrow cells are infused before transplantation. (AU)