BACKGROUND: With adequate immunosuppression the majority of renal allografts are accepted, despite the exceptional vigour of the T cell alloimmune response. Previous work from this laboratory has demonstrated that this is accompanied by significant reductions in the precursor frequencies of anti-donor T cells. We have also shown that parenchymal cells are tolerogenic in vitro. We propose that the reduction in T cell frequencies may be due to the interaction between circulating T cells and potentially tolerogenic graft parenchymal cells. Primed/memory T cells (CD45RO+) are the only subset capable of reaching the allograft and therefore we would predict that T cell hyporesponsiveness would develop predominantly in the CD45RO+ subset due to their trafficking properties. METHODS: Frequencies of IL-2 secreting CD45RA+ and CD45RO+ CD4+ T cells in response to donor and third party stimulator cells were estimated in a series of renal transplant recipients, both before and after transplantation. RESULTS: There were highly significant reductions in the frequencies of donor-specific CD4+CD45RO+ T cells, when adjusted to control for the generalised effects of immunosuppression. There were no significant alterations in the frequencies of donor-specific CD4+CD45RA+ T cells. CONCLUSIONS: In renal transplant recipients, donor-specific CD4+ T cell hyporesponsiveness occurs predominantly in CD4+ CD45RO+ T cells which is the subset capable of trafficking through the graft.
BACKGROUND: With adequate immunosuppression the majority of renal allografts are accepted, despite the exceptional vigour of the T cell alloimmune response. Previous work from this laboratory has demonstrated that this is accompanied by significant reductions in the precursor frequencies of anti-donor T cells. We have also shown that parenchymal cells are tolerogenic in vitro. We propose that the reduction in T cell frequencies may be due to the interaction between circulating T cells and potentially tolerogenic graft parenchymal cells. Primed/memory T cells (CD45RO+) are the only subset capable of reaching the allograft and therefore we would predict that T cell hyporesponsiveness would develop predominantly in the CD45RO+ subset due to their trafficking properties. METHODS: Frequencies of IL-2 secreting CD45RA+ and CD45RO+ CD4+ T cells in response to donor and third party stimulator cells were estimated in a series of renal transplant recipients, both before and after transplantation. RESULTS: There were highly significant reductions in the frequencies of donor-specific CD4+CD45RO+ T cells, when adjusted to control for the generalised effects of immunosuppression. There were no significant alterations in the frequencies of donor-specific CD4+CD45RA+ T cells. CONCLUSIONS: In renal transplant recipients, donor-specific CD4+ T cell hyporesponsiveness occurs predominantly in CD4+ CD45RO+ T cells which is the subset capable of trafficking through the graft.
Authors: L Cherkassky; M Lanning; P N Lalli; J Czerr; H Siegel; L Danziger-Isakov; T Srinivas; A Valujskikh; D A Shoskes; W Baldwin; R L Fairchild; E D Poggio Journal: Am J Transplant Date: 2011-05-12 Impact factor: 8.086
Authors: Mobin A Karimi; Jerrod L Bryson; Lee P Richman; Andrew D Fesnak; Theresa M Leichner; Atsushi Satake; Robert H Vonderheide; David H Raulet; Ran Reshef; Taku Kambayashi Journal: Blood Date: 2015-03-18 Impact factor: 22.113
Authors: Y Yamada; S Boskovic; A Aoyama; T Murakami; P Putheti; R N Smith; T Ochiai; O Nadazdin; I Koyama; O Boenisch; N Najafian; M K Bhasin; R B Colvin; J C Madsen; T B Strom; D H Sachs; G Benichou; A B Cosimi; T Kawai Journal: Am J Transplant Date: 2011-11-04 Impact factor: 8.086