ABSTRACT
Studies of allotolerance in animal models do not usually consider the presence of preexisting memory T cells and activated immune status. However, humans are exposed throughout life to a multitude of external agents that enhance the immune memory. In this article, we consider the effect that a previous kidney transplant has on the number of regulatory T cells (Tregs), effector memory T cells (TEM), and central memory T cells (TCM). Sixty-three patients with end-stage renal disease were studied just before being transplanted (51 first transplants and 12 retransplants). The numbers of Tregs (CD4+ CD25highCD127lowCD27+CD62L+CD45RO+FOXP3+), TEM (CD3+CD45RO+CD62L+), and TCM (CD3+CD45RO+CD62L-) cell subsets were quantified in peripheral blood by flow cytometry. The absolute number of Tregs was slightly lower in patients with previous allografts (median, 95% confidence interval [CI]: 16.7 cells/mm3, 12-20.5) than in those who received their first transplants (median, 95% CI: 19.6 cells/mm3, 19.3-29.6; P-NS). Clearer differences were found with the number of CD3+ TCM, since the transplanted patients had lower numbers (238 cells/mm3, 153-323) than those who had not yet received transplants (378 cells/mm3, 317-439; P=.029). As a result, the TEM/TCM ratios of both CD4+ and CD8+ T cells in patients with previous allografts were higher than in those who received first transplants. In conclusion, the assessment of just the number of Tregs in renal transplant patients is not enough and must be read together with the number of TEM and TCM. The TEM:TCM ratio increases in patients with previous allografts, probably due to activation of the immune response in renal transplantation.
