Evaluation of T-cell receptor repertoires in patients with long-term renal allograft survival.
The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (> or = 9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vss usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR V beta families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells.
Alvarez
Cristiam M
CM
Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia.
Opelz
Gerhard
G
Giraldo
Mabel C
MC
Pelzl
Steffen
S
Renner
Fabrice
F
Weimer
Rolf
R
Schmidt
Jan
J
Arbeláez
Mario
M
García
Luis F
LF
Süsal
Caner
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006435:Renal Dialysis; D013997:Time Factors; D014184:Transplantation, Homologous
D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell