T cell homeostasis after ATG induced lymphocytopenia in renal transplant patients; studied through in vivo 2H2O labeling

Patients who have received a renal allograft are treated with maintenance
immuosuppressive drug therapy, consisting of prednisolone, tacrolimus and
mycophenolate mofetil. When their clinical course is complicated by an acute
humoral graft rejection, they are treated with a course of Anti-Thymocyte
Globulin for 14 days. As a consequence, the T cell pool rapidly becomes
depleted. This T cell depletion is known to show a slow recovery. Especially
the CD4+ naïve cells fail to recover completely, whereas the CD8+ naïve cells
very slowly recuperate to pre-treatment values. A possible explanation for this
difference in recovery might be that the CD4+ naïve T cells rely more on the
thymus and CD8+ naïve cells rely more on homeostatic proliferation. In previous
studies with 2H2O labelling of lymphocytes in healthy volunteers however, CD4+
naïve T-cells were shown to have a higher production rate than CD8+ naïve T
cells.
Through in vivo labelling of lymphocytes with 2H2O , we believe to discover
more about the T cell - and especially naïve T cell homeostasis in the
lymphopenic situation after ATG treatment. By in vivo labelling the cells of
renal transplant patients who receive standard maintenance immunosuppressive
therapy and who were not treated with ATG, we can control for any effect of
standard maintenance immunosuppressive drug therapy on the T-cell homeostasis.

To get more insight into the T cell homeostasis in lymfocytopenic, ATG treated
patients and normocytopenic patients treated with standard maintenance
immunosuppressive drug therapy.

Participants will be labelled with 2H2O for a period of 9 weeks, with a
downlabelling period of 21 weeks. Using gas chromatography mass spectrometry,
2H2O within different subsets of sorted T cells will be measured.

Blood and urine samples will be collected before 2H2O labelling, at week 2 or
3, week 5 or 6, week 9, week 11, week 14, week 18 and week 30 after labelling.
This will in total be 8 x 56ml blood.
According to literature and previous studies, in vivo isotope labelling with
2H2O is harmless. Patients are admitted into the hospital for observation
during initial oral administration of 2H2O, because rare adverse effects of
transient vertigo or dizziness have been reported