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Titolo:
Loss of direct and maintenance of indirect alloresponses in renal allograft recipients: Implications for the pathogenesis of chronic allograft nephropathy
Autore:
Baker, RJ; Hernandez-Fuentes, MP; Brookes, PA; Chaudhry, AN; Cook, HT; Lechler, RI;
Indirizzi:
Hammersmith Hosp, Imperial Coll, Dept Immunol, Fac Med, London W12 0NN, England Hammersmith Hosp London England W12 0NN Fac Med, London W12 0NN, England Hammersmith Hosp, Imperial Coll, Dept Renal Med, Fac Med, London W12 0NN, England Hammersmith Hosp London England W12 0NN Fac Med, London W12 0NN, England Hammersmith Hosp, Imperial Coll, Dept Histopathol, Fac Med, London W12 0NN, England Hammersmith Hosp London England W12 0NN Fac Med, London W12 0NN, England
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 12, volume: 167, anno: 2001,
pagine: 7199 - 7206
SICI:
0022-1767(200112)167:12<7199:LODAMO>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
TOTAL LYMPHOID IRRADIATION; LIMITING DILUTION ASSAYS; MIXED LEUKOCYTE REACTION; PRIMERS PCR-SSP; CHRONIC REJECTION; T-CELLS; SUBCLINICAL REJECTION; TRANSPLANT RECIPIENTS; KIDNEY ALLOGRAFTS; GRAFT-REJECTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Lechler, RI Hammersmith Hosp, Imperial Coll, Dept Immunol, Fac Med, Du Cane Rd, LondonW12 0NN, England Hammersmith Hosp Du Cane Rd London England W12 0NN N, England
Citazione:
R.J. Baker et al., "Loss of direct and maintenance of indirect alloresponses in renal allograft recipients: Implications for the pathogenesis of chronic allograft nephropathy", J IMMUNOL, 167(12), 2001, pp. 7199-7206

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 tothis 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 longstandingrenal 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 18:20:52