Enliven: Surgery and Transplantation

The Role of Induction Therapy in Heart Transplant. Is it Obligatory?
Author(s): DR. G Ramasubrahmanyam, MS, MCh

Rejection is the major cause of early morbidity and mortality post heart transplantation. Immunologic mechanisms are responsible for causing graft rejection, which can occur in various ways. The rejection is primarily a T-lymphocyte (T cell) mediated event, although humoral (B-cell) responses also contribute. Hyperacute rejection occurs when preformed antibodies to human leukocyte antigens (HLA) develop resulting in an immediate rejection. The recognition of donor antigens begins with the function of antigen presenting cells (APCs). Donor APCs are expressed as donor alloantigens which are directly recognized by recipient T-cells which is known as direct allorecognition. When the donor alloantigens are shed by the graft which are taken up by the recipient APCs and then presented to T-cells, which is known as indirect allorecognition. These alloantigens are recognized by the T-cell receptor (TCR) CD-3 complex on the surface of T-cell. But the levels of T-cell activation to cause a rejection occurs only when there is a second or a co-stimulatory signal between APC and T-cell. There are several co-stimulatory molecules that function as receptor ligand pairs on APC and T-cell surface. Engagement of the TCR-CD3 complex, followed by co-stimulatory signals, results in activation of calcineurin in the cytoplasm of the T-cell. The nuclear factor of activated T-cell (NF-AT) is transcribed by the dephosphorylated calcineurin which then binds to interleukin 2 (IL-2) in the nucleus which activates the cell surface IL-2 receptor. This stimulates clonal expansion of T helper cells, cytotoxic T cells, B cells and natural killer cells. Engagement of the IL-2R activates the enzyme target of rapamycin (TOR). TOR regulates the translation of mRNAs to proteins