PERFORIN AND GRANZYME-B - PREDICTIVE MARKERS FOR ACUTE GVHD OR CARDIAC REJECTION AFTER BONE-MARROW OR HEART-TRANSPLANTATION

Monitoring of human allografts requires to use histological, immunohis tochemical and functional techniques to characterize graft infiltratin g cells. Granzyme B and perforin gene expression is of major importanc e in functional studies. Those proteins are present in the cytoplasmic granules of cytotoxic t lymphocytes and are secreted during granule e xocytosis at the effector/target cell interface. Gene expression of bo th proteins has been studied by in situ hybridization using specific r iboprobes on serial sections of biopsies in two pathological models. O ur results show that cells infiltrating early skin lesions of patients with acute GVHD after bone marrow graft are exclusively composed of T cells, among which some of them express granzyme B and perforin genes . Similarly the presence of granzyme B and perforine-expressing cells in endomyocardial biopsies of heart transplanted patients has been ass ociated to early and severe crisis of rejection. In contrast, the abse nce of functional markers in lymphoid infiltrates was coinciding with less aggressive and late episodes of rejection. Taken together, our da ta indicate that granzyme B and perforin gene expression in skin infil trating lymphocytes during GVH or within heart infiltrating cells duri ng crisis of rejection are in favor of severe processes. The study has allowed to predict during heart transplantation the apparition of a r ejection crisis and to show the necessity for treating the patient wit h immunsuppresive drugs. This is also the case for patients with GVHD at the time of the first skin rash.