Immunological monitoring of renal transplant recipients to predict acute allograft rejection following the discontinuation of tacrolimus.
BACKGROUND
Transplant patients would benefit from reduction of immunosuppression providing that graft rejection is prevented. We have evaluated a number of immunological markers in blood of patients in whom tacrolimus was withdrawn after renal transplantation. The alloreactive precursor frequency of CD4+ and CD8+ T cells, the frequency of T cell subsets and the functional capacity of CD4+CD25+FoxP3+ regulatory T cells (Treg) were analyzed before transplantation and before tacrolimus reduction. In a case-control design, the results were compared between patients with (n = 15) and without (n = 28) acute rejection after tacrolimus withdrawal.


RESULTS
Prior to tacrolimus reduction, the ratio between memory CD8+ T cells and Treg was higher in rejectors compared to non-rejectors. Rejectors also had a higher ratio between memory CD4+ T cells and Treg, and ratios <20 were only observed in non-rejectors. Between the time of transplantation and the start of tacrolimus withdrawal, an increase in naive T cell frequencies and a reciprocal decrease of effector T cell percentages was observed in rejectors. The proportion of Treg within the CD4+ T cells decreased after transplantation, but anti-donor regulatory capacity of Treg remained unaltered in rejectors and non-rejectors.


CONCLUSIONS
Immunological monitoring revealed an association between acute rejection following the withdrawal of tacrolimus and 1) the ratio of memory T cells and Treg prior to the start of tacrolimus reduction, and 2) changes in the distribution of naive, effector and memory T cells over time. Combination of these two biomarkers allowed highly specific identification of patients in whom immunosuppression could be safely reduced.
Kreijveld
Ellen
E
Department of Blood Transfusion and Transplantation Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Koenen
Hans J P M
HJ
van Cranenbroek
Bram
B
van Rijssen
Esther
E
Joosten
Irma
I
Hilbrands
Luuk B
LB
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006084:Graft Rejection / Q000175:diagnosis*; D006801:Humans; D007107:Immune System; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods*; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D016559:Tacrolimus