Analysis of the peripheral T-cell repertoire in kidney transplant patients.
Miqueu P., Degauque N., Guillet M., Giral M., Ruiz C., Pallier A., Braudeau C., Roussey-Kesler G., Ashton-Chess J., Doré J-C., Thervet E., Legendre C., Hernandez-Fuentes MP., Warrens AN., Goldman M., Volk H-D., Janssen U., Wood KJ., Lechler RI., Bertrand D., Sébille V., Soulillou J-P., Brouard S.
The long-term stability of renal grafts depends on the absence of chronic rejection. As T cells play a key role in rejection processes, analyzing the T-cell repertoire may be useful for understanding graft function outcomes. We have therefore investigated the power of a new statistical tool, used to analyze the peripheral blood TCR repertoire, for determining immunological differences in a group of 229 stable renal transplant patients undergoing immunosuppression. Despite selecting the patients according to stringent criteria, the patients displayed heterogeneous T-cell repertoire usage, ranging from unbiased to highly selected TCR repertoires; a skewed TCR repertoire correlating with an increase in the CD8(+) /CD4(+) T-cell ratio. T-cell repertoire patterns were compared in patients with clinically opposing outcomes i.e. stable drug-free operationally tolerant recipients and patients with the "suspicious" form of humoral chronic rejection and were found significantly different, from polyclonal to highly selected TCR repertoires, respectively. Moreover, a selected TCR repertoire was found to positively correlate with the Banff score grade. Collectively, these data suggest that TCR repertoire categorization might be included in the calculation of a composite score for the follow-up of patients after kidney transplantation.