The effect of immunosuppressive therapy on T-cells after kidney transplantation

Zybleva S. , Zyblev S., Novikov P.

The Republican Research Center for Radiation medicine and Human Ecology, Gomel, Belarus
Gomel State Medical University, Gomel, Belarus
Vitebsk State Medical University, Vitebsk, Belarus

Objective: to study the effect of immunosuppressive therapy on CD3+CD4+CD25+ (T-helper activated) and CD3+CD4+CD25+highCD127+low (T-regulatory) lymphocytes in the recipients of the renal allograft.
Materials and Methods: the quantity of CD3+CD4+CD25+ and CD3+CD4+CD25+highCD127+low was determined in the peripheral blood of 43 recipients of the renal allograft with normal renal function by flow cytofluorometry method on day 0, 1, 3, 10, 30, 90, 180, 360. All the patients received induction therapy with anti-CD25 monoclonal antibodies and three component immunosuppressive therapy, including calcineurin inhibitors, antiproliferative drugs (mycophenolate or azathioprine), and corticosteroids.
Results. There wasn’t detected any significant differences of the quantity of CD3 +CD4 +CD25 + and CD3+CD4+CD25+highCD127+low lymphocyte subpopulation in the group in the group of patients before kidney transplantation and in the group of healthy patients. On the first day after kidney transplantation the level of CD3+CD4+CD25+ and
CD3+ CD4+ CD25+highCD127+low lymphocyte subpopulation was significantly decreased. The maximum decrease of quantity of CD3+CD4+CD25+ cells was detected on the 10th day of followup. (р0,10Wilcoxon Matched Pairs Test=0,018; Z=2,38) with the subsequent progressive growth of this subpopulation, and the decrease from the 3rd to the 10th day was no longer significant (р10,30 Wilcoxon Matched Pairs Test=0,332; Z=0,986). In addition, the tendency to decrease in CD3+CD4+CD25+highCD127+low persisted for
a longer period (up to 30 days). On the 90th day after the surgery the quantity of CD3+CD4+CD25+ (р0,90 Wilcoxon Matched Pairs
Test=0,600, Z=0,524) and CD3+CD4+CD25+highCD127+low (р0,90
Wilcoxon Matched Pairs Test=0,248, Z=1,153) didn’t differ from the level
before transplantation. On the 360th day of the follow-up, there was detected a decrease in T-regulatory lymphocytes compared to the group of healthy patients (рMann-Whitney U Test=0,038; Z=-2,071).
Conclusion. The duration of the almost complete blocking of the IL-2 receptor on lymphocytes in patients after kidney transplantation receiving immunosuppressive therapy induction therapy with anti-CD25 monoclonal antibodies and three-component therapy with calcineurin inhibitors,antiproliferative drugs (mycophenolate or azathioprine) andcorticosteroids is about 3 months. This should be taken into
account when interpreting the results of an immunological examination of patients of this category. The quantity decrease in CD3+CD4+CD25+highCD127+low cells at the 12th month of follow-up may be one of the effects of calcineurin inhibitors and it can adversely affect the formation and maintenance of immunological tolerance in the posttransplant period.