Role Of Cytokines In Graft Versus Host Disease After Peripheral Blood Stem Cell Transplantation ( PBSCT )

Abstract

Summary Allogenic HSCT is a widely used therapeutic modality. Acute GVHD is one of the most important complications of HSCT. It is a direct result of one of the principal functions of the immune system: the distinction of self from non self as immune competent cells may be transplanted from donor to the patient. These donor (graft) cells may recognize patient (host) cells as foreign, which may lead to GVHD. GVHD pathophysiology is complex, but is critically dependent on the recognition of host MHC and/ or minor histocompatibility antigens on host APCs by the naive donor T cells. This is followed by differentiation of donor T cells primarily into Thl cells, which secrets IFNy, TNF, and IL2, leading to increased expression of numerous molecules involved in GVHD, including adhesion molecules, chemokines, major histocompatabililty complex antigens. As a result there is enhanced antigen presentation· leading to recruitment of effector cells which secrete cytokines into target organs leading to more organ damage during GVHD. Several reports have high lightened the critical role of cytokines released during the 'cytokine storm' in amplifying acute GVHD. The aim of the work was to develop an experimental setup to mimic the response of the immune cells of the graft to the host antigens as reflected by cytokine production. The final aim was to correlate the cytokine pattern to the development of acute GVHD and verify if this pattern could possibly predict the occurrence of acute GVHD