Skew in T-cell receptor usage and clonal T-cell expansion in patients with chronic rejection of transplanted kidneys.
BACKGROUND
It is not known whether alloreactive T cells are involved in chronic rejection of transplanted kidneys. The aim of the present study was to determine the involvement of T cells in the chronic graft rejection.


METHODS
T-cell receptor (TCR) variable region alpha-chain and TCR variable region beta-chain repertoires were analyzed in peripheral blood mononuclear cells. T-cell clonalities were analyzed by complementarity-determining region 3 size spectratyping.


RESULTS
A significant increase in the frequencies of one or more TCR variable region alpha-chain and TCR variable region beta-chain segments was detected in 13 and 15 of the 24 kidney transplant recipients, respectively. The extent of the skew in the TCR usage was correlated with the levels of clonal T-cell expansion, indicating that the clonally expanding T cells were responsible for the skew in the TCR usage. The levels of the skew in the TCR usage and clonal T-cell expansion were significantly greater in the recipients with a graft failure than in those with a stable graft function ( P=0.0081 and P=0.012, respectively). These results indicate that the clonally expanding T cells in the periphery may be related to graft rejection. The percent increase in the serum creatinine levels, which reflected the deterioration of the kidney functions, was significantly higher in the recipients who showed high levels of clonal T-cell expansion than in those who did not ( P=0.021).


CONCLUSIONS
The results demonstrate that clonal T-cell expansion in the periphery has a negative impact on the long-term graft functions, and that analysis of the clonal T-cell expansion in peripheral blood mononuclear cells provide significant information on the fate of the transplanted kidney.
Matsutani
Takaji
T
Department of Medical Science, Discovery Research Laboratories, Shionogi Research Laboratories, Shionogi and Co., Ltd., Osaka, Japan. takaji.matsutani@shionogi.co.jp
Ohashi
Yoichi
Y
Yoshioka
Takeshi
T
Tsuruta
Yuji
Y
Doi
Hideyuki
H
Satomi
Susumu
S
Suzuki
Ryuji
R
D000293:Adolescent; D000328:Adult; D002648:Child; D002908:Chronic Disease; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000276:immunology; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000276:immunology; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003404:Creatinine