The role of the allograft in the induction of donor-specific T cell hyporesponsiveness.
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.
Baker
R J
RJ
Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Hernandez-Fuentes
M P
MP
Brookes
P A
PA
Chaudhry
A N
AN
Lechler
R I
RI
D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D009000:Monocytes / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology
D007376:Interleukin-2; D017493:Leukocyte Common Antigens