Recent studies have shown that CD4+ CD25+ T cells belong to two functionally
different T lymphocytes, i.e. regulatory T cells (Treg) or activated T cells (Tact),
which can be distinguished based on the expression of CD45RO and IL-7R:
Treg (FoxP3+) are CD45RO+ IL-7R- , whereas Tact (FoxP3- ) are CD45RO+ IL-
7R+.
In order to determine if a CD4+ CD25+ CD45RO+ IL-7R+ activated T cell population
might be identified in kidney transplant recipients, we studied 27 healthy
subjects (HS) and 23 kidney recipients, of whom 17 had stable graft function
under standard immunosuppression (IS), 5 had biopsy-proven chronic humoral
rejection (CHR), and one was a stable "tolerant" patient who had discontinued
IS for more than 2 years. Phenotypical analysis by flow cytometry and functional
assays by MLR were performed.
Overall, the Tact population was found to be significantly increased in 87% of
the transplant recipients (mean: 18.8±10.1% of CD4+ CD25+ T cells) compared
to HS (mean: 4.5±2.0%; P<0.0001). In the 5 patients with CHR, this
Tact population was highly expanded (31.3±9.3%; P<0.0001), whereas it
was comparable to HS in the "tolerant" recipient (4.7%). Intermediate levels
(16.0±6.9%; P<0.0001) were found in the 17 stable recipients. In CHR, the
proliferative capacity of the Tact population was found to be 5-fold higher when
stimulated by irradiated donor PBMC as compared to a stimulation by irradiated
3rd party PBMC.
After kidney transplantation, an expanded circulating CD4+ CD25+ T cell population
characterized by the expression of CD45RO and IL-7R was found in
most recipients, particularly in those with CHR. In a patient with long-term
operational tolerance, this Tact population was similar to HS. Measuring circulating
Tact may become a useful monitoring tool after transplantation