**1. Introduction**

Tolerance in human transplantation can be defined in two ways [1]. Clinical tolerance (also referred to as clinical operational tolerance [2]) is the survival of a foreign organ or tissue (allogeneic or xenogeneic) in a normal recipient in the absence of immunosuppression [1]. Immune tolerance is the absence of a detectable immune response against a functional organ or tissue in the absence of immunosuppression [1].

Early evidence demonstrating that adult mice could be tolerant of skin grafts after the induction of neonatal tolerance by the introduction of splenocytes intraperitoneally was shown by Brent and Medawar, in 1953 [3]. The central role of the thymus in mediating cellular immunity and graft rejection was established by JFAP Miller, who showed that nude mice tolerated skin allografts because of a marked deficiency of lymphocytes [4]. Conversely, there have been recent studies that show that spleen transplantation in pigs or dogs has a tolerogenic effect on renal transplantation [5, 6]. On the basis of the promising results obtained in these animal models, several tolerogenic protocols have been attempted in humans, but most have failed to achieve robust and stable tolerance after renal transplantation. This is due to that the transplantation immunobiology is very complex, because of the involvement of several components such as antibodies, antigen presenting cells, helper and cytotoxic T cell subsets, immune cell, surface molecules, signaling mechanisms and cytokines; which play a role in the alloimmune response.
