Geriatric anti-donor T-cell activity and development of alloreactive long-term hypo-responsive T cell function (GANDALF); Post-transplant development of anti-donor-specific hypo-responsiveness; Lessons to be learned from older kidney transplant recipients

In the majority of kidney transplant recipients with stable graft function,
anti-donor T-cell reactivity is absent long after transplantation (>5 years) as
reflected by a decreased proliferative response of recipient T cells to donor
antigen presenting cells, a phenomenon referred to as donor-specific
hypo-responsiveness (DSH). The mechanism(s) underlying this phenomenon are
unclear and may involve deletion of anti-donor reactive T cells, active
suppression of anti-donor reactive T cells by regulatory T cells or induction
of anergy in these anti-donor reactive T cells. Kidney transplant recipients
on the waiting list for kidney transplantation have a prematurely aged T cell
compartment accompanied by a compromised T cell-mediated immunity. This may
partly explain the clinical observation that older recipients (> or equal to 55
yrs) are more prone to develop DSH relatively early after transplantation. We
hypothesize that a general principle of DSH development is operative in
recipients of a donor kidney which can be revealed by studying the phenotype
and function of alloreactive T cells of recipients at different time-points
after transplantation, comparing the elderly with young recipients.

To identify the mechanism(s) of DSH by analysis of post-transplant kinetics of
phenotype and function of alloreactive CD4+ and CD8+ T cells.

This is an investigator-driven, observational (cross-sectional and
longitudinal) study comparing features of anti-donor T-cell reactivity at
different time-points after transplantation.

Participation in the cross-sectional part of the trial consists of one
additional blood donation (7 heparin tubes a 7 mL blood= 49 mL of blood) at the
time of routine blood withdrawal prior to, 3-5, 5-10, 10-15, 15-20 or >20 years
following transplantation. The biobank *Niertransplantatie (versie 2, 29
februari 2012)* contains material of both the recipient as well as the donor
prior to transplantation for which we have obtained permission to use for this
research purpose.

Participation in the longitudinal part of the trial consists of 5 blood
donations (5 times 7 heparin tubes a 7 mL blood= 245 mL) prior to and at
different intervals after transplantation, i.e. 3 and 6 months and 1 and 3
years after transplantation during a regular visit at the outpatient clinic.
The corresponding donor will be asked to participate at the time of donation of
the kidney and blood (7 heparin tubes a 7 mL blood=49 mL) will be drawn at the
time of routine blood withdrawal. The burden for the patient (and donor) is
minimal and no additional risks are involved when participating in this study.
Participation in this study does not compose of a direct advantage for this
patient but contributes to the increased knowledge obtained with respect to
kinetics of donor-specific hypo-responsiveness following transplantation.
Furthermore, this may facilitate individualizing immunosuppressive regimes
thereby minimizing adverse effects of long term use and prolonging graft and
patient survival.