Although important progresses have been achieved in the therapeutic management of
transplant recipients, acute and chronic rejections remain the leading causes of premature
graft loss after solid organ transplantation. This, together with the undesirable side effects
of immunosuppressive drugs, has significant implications for the long-term outcome of
transplant recipients. Thus, a better understanding of the immunological events occurring
after transplantation is essential.
The immune system plays an ambivalent role in the outcome of a graft. On one hand,
some T lymphocytes with effector functions (called alloreactive) can mediate a cascade of
events eventually resulting in the rejection, either acute or chronic, of the grafted organ ;
on the other hand, a small subset of T lymphocytes, called regulatory T cells, has been
shown to be implicated in the control of these harmful rejection responses, among other
things. Thus, we focused our interest on the study of the balance between circulating
effectors (alloreactive) and regulatory T lymphocytes, which seems to play an important
role in the outcome of allografts, in the context of kidney transplantation. The results were
correlated with various variables such as the clinical status of the patients, the
immunosuppressive drugs used as induction or maintenance agents, and past or current
episodes of rejection. We observed that the percentage of the alloreactive T lymphocyte
population was correlated with the clinical status of the kidney transplant recipients.
Indeed, the highest percentage was found in patients suffering from chronic humoral
rejection, whilst patients on no or only minimal immunosuppressive treatment or on
sirolimus-based immunosuppression displayed a percentage comparable to healthy
non-transplanted individuals. During the first year after renal transplantation, the balance
between effectors and regulatory T lymphocytes was tipped towards the detrimental
effector immune response, with the two induction agents studied (thymoglobulin and
basiliximab).
Overall, these results indicate that monitoring these immunological parameters may be
very useful for the clinical follow-up of transplant recipients ; these tests may contribute to
identify patients who are more likely to develop rejection or, on the contrary, who tolerate
well their graft, in order to adapt the immunosuppressive treatment on an individual basis.