Overcoming memory T-cell responses for induction of delayed tolerance in nonhuman primates Academic Article uri icon

Overview

MeSH Major

  • Bone Marrow Transplantation
  • Graft Survival
  • Immunologic Memory
  • Kidney Transplantation
  • T-Lymphocytes
  • Transplantation Chimera
  • Transplantation Tolerance

abstract

  • The presence of alloreactive memory T cells is a major barrier for induction of tolerance in primates. In theory, delaying conditioning for tolerance induction until after organ transplantation could further decrease the efficacy of the regimen, since preexisting alloreactive memory T cells might be stimulated by the transplanted organ. Here, we show that such "delayed tolerance" can be induced in nonhuman primates through the mixed chimerism approach, if specific modifications to overcome/avoid donor-specific memory T-cell responses are provided. These modifications include adequate depletion of CD8+ memory T cells and timing of donor bone marrow administration to minimize levels of proinflammatory cytokines. Using this modified approach, mixed chimerism was induced successfully in 11 of 13 recipients of previously placed renal allografts and long-term survival without immunosuppression could be achieved in at least 6 of these 11 animals.

publication date

  • February 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3268945

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2011.03795.x

PubMed ID

  • 22053723

Additional Document Info

start page

  • 330

end page

  • 40

volume

  • 12

number

  • 2