Loss of direct and maintenance of indirect alloresponses in renal allograft recipients: implications for the pathogenesis of chronic allograft nephropathy.
J Immunol
; 167(12): 7199-206, 2001 Dec 15.
Article
de En
| MEDLINE
| ID: mdl-11739543
ABSTRACT
Chronic allograft nephropathy (CAN) is the principal cause of late renal allograft failure. This complex process is multifactorial in origin, and there is good evidence for immune-mediated effects. The immune contribution to this process is directed by CD4(+) T cells, which can be activated by either direct or indirect pathways of allorecognition. For the first time, these pathways have been simultaneously compared in a cohort of 22 longstanding renal allograft recipients (13 with good function and nine with CAN). CD4(+) T cells from all patients reveal donor-specific hyporesponsiveness by the direct pathway according to proliferation or the secretion of the cytokines IL-2, IL-5, and IFN-gamma. Donor-specific cytotoxic T cell responses were also attenuated. In contrast, the frequencies of indirectly alloreactive cells were maintained, patients with CAN having significantly higher frequencies of CD4(+) T cells indirectly activated by allogeneic peptides when compared with controls with good allograft function. An extensive search for alloantibodies has revealed significant titers in only a minority of patients, both with and without CAN. In summary, this study demonstrates widespread donor-specific hyporesponsiveness in directly activated CD4(+) T cells derived from longstanding recipients of renal allografts, whether they have CAN or not. However, patients with CAN have significantly higher frequencies of CD4(+) T cells activated by donor Ags in an indirect manner, a phenomenon resembling split tolerance. These findings provide an insight into the pathogenesis of CAN and also have implications for the development of a clinical tolerance assay.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Lymphocytes T CD4/
/
Transplantation rénale
/
Tolérance à la transplantation
/
Rejet du greffon
/
Isoantigènes
/
Maladies du rein
Type d'étude:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limites:
Adult
/
Humans
/
Middle aged
Langue:
En
Journal:
J Immunol
Année:
2001
Type de document:
Article
Pays d'affiliation:
Royaume-Uni