Paradigm Shift to Tolerance from Conventional Immunosuppression in Renal Transplant: A Basic Strategy through Lymphocyte Depletion

The current immunosuppressive protocols for renal allograft management, targets mainly the resident and host lymphocytes that come into play to reject the grafted tissue. This is analogous to use of antibiotics against invading microorganisms. This strategy is incomplete as the allograft under goes acute rejection episodes, and long term chronic rejection along with many of the adverse events associated with immunosuppressive medicines.
On the other hand, transplant tolerance is defined as a state of donor-specific unresponsiveness to the allograft without a need for ongoing pharmacologic immunosuppression or with a minimal use of single or dual agents. This is a paradigm shift in the allograft management. Even though impossible to achieve currently, anecdotal reports showing complete or partial tolerance do appear in the literature. In summary, that happens through lymphocyte depletion to a degree that provides tolerance.
In theory and practice, there are three strategies of achieving tolerance: (a) achieving a state of hematological chimera, which can induce complete tolerance, (b) more recent, prope or near tolerance where immune-reactive T-cells are eliminated or inhibited using monoclonal antibodies, and (c) most recent, research-based Chimeric Antigen Receptor for T-regulatory (CAR-T) cell therapy using genetically engineered T-reg cells, targeting specific T-Cell Receptors (TCR) for attenuation of Tcell immune-reactivity, which induces energy.
Safe and reliable strategies for the induction of full tolerance have not yet been achieved. However, in the light of currently available anecdotal and prospective randomized studies, a plausible paradigm shift to tolerance could be anticipated in near future.
This review article would address the possible strategies, indications and applicability of inducing tolerance by lymphocyte depletion.