Terminally differentiated CD8+ Temra cells are associated with the risk for acute kidney allograft rejection.
BACKGROUND
End-stage renal disease (ESRD) is associated with T-cell dysregulation, leading to a variable degree of lymphopenia and increased T-cell differentiation. This may cause a relevant reduction in T-cell immunity, yielding a lowered risk for acute rejection (AR) of kidney allografts.


METHODS
Before kidney transplantation, circulating CD4 and CD8 T-cell differentiation was established by determining the frequency of naive T cells, central memory and effector memory T cells, and the highly differentiated CD8 Temra cells. In addition, the frequency of differentiated T cells without expression of the costimulatory molecule CD28 was measured.


RESULTS
In 47 patients of the 185 patients included, a biopsy-proven AR occurred. Compared with healthy controls, T cells of patients with ESRD were significantly more differentiated. Patients with AR showed the least signs of T-cell dysregulation with significantly more T cells, more naive T cells, and less terminal differentiation of memory T cells compared with nonrejecting patients. After multivariate analysis, only the frequency of terminally differentiated CD8 Temra cells (per percent, 4% decrease of risk [P=0.006]; per tertile, 34% decrease in risk [P=0.002]) and the number of human leukocyte antigen mismatches (per mismatch, 33% [P=0.005]) predicted the risk for AR. Functional analysis showed that CD8 Temra cells have a highly proinflammatory and cytotoxic profile. In vitro T-cell proliferation assays did not reveal a suppressor function of these cells.


CONCLUSIONS
Advanced ESRD-related T-cell dysregulation that is associated with a relative increase of terminally differentiated CD8 Temra cells protects against AR after kidney transplantation.
Division of Nephrology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. M.G.H.Betjes@erasmusmc.nl
Michiel G H
MG
Betjes
Ruud W J
RW
Meijers
Elly A
EA
de Wit
Willem
W
Weimar
Nicolle H R
NH
Litjens
D000208:Acute Disease; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D006084:Graft Rejection / Q000209:etiology*; D006650:Histocompatibility Testing; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000401:mortality; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D014184:Transplantation, Homologous