T-cell selection and T-cell receptor variable beta-chain usage in chronic hemodialysis patients.

Thymic and extrathymic selection processes are responsible for the shape of the T-cell repertoire. T-cell receptor (TCR) variable (V) chain usage, holding a place in tolerance, autoimmunity and response to external agents, was analyzed in 41 patients maintained on chronic hemodialysis treatment. Leukocyte (mean: 6444 +/- 2277 cells/microliters), lymphocyte (mean: 1457 +/- 707 cells/microliters) and T-cell (mean: 67 +/- 16%) counts were within expected limits, but hemodialysis patients showed an impressive increase of TCR V beta 6.7 positive peripheral blood lymphocytes (PBL) and a massive deletion of TCR V beta 8 positive PBL. V beta 6.7 positive PBL were detectable in all hemodialysis patients (n = 41, mean: 2.47 +/- 1.61% PBL) in contrast to a healthy population, where only 45% of subjects expressed V beta 6.7 on PBL (n = 9, mean: 3.50 +/- 1.83% PBL). Only 27% of our hemodialysis patients expressed V beta 8 on PBL (n = 11, mean: 1.00 +/- 1.94% PBL) in contrast to healthy subjects, who presented V beta 8 positive PBL (n = 20, mean: 2.89 +/- 1.23% PBL) in every case. Neither primary kidney disease, nor response to vaccination for hepatitis-B, nor dialyzer membranes used, were associated with these alterations of the TCR V beta-pool. It is likely, that the well-known impairment of the cytokine network in chronic renal failure, uremic toxins or response to infectious agents, may contribute to these different and possibly independent T-cell selection mechanisms in uremia.