HEAT-SHOCK PROTEIN-INDUCED T-LYMPHOCYTE PROPAGATION FROM ENDOMYOCARDIAL BIOPSIES IN HEART-TRANSPLANTATION

Background: Recent studies have shown that heat shock proteins can be recognized by T cells during various immunologically mediated inflamma tory processes. Injurious stimuli to cells induce an increased product ion of heat shock proteins which could lead to their cell surface expr ession and subsequent recognition by the immune system. We have postul ated that allograft infiltrating cells may recognize heat shock protei ns, especially during rejection. Methods: This hypothesis was tested b y incubating heart transplant biopsy specimens from 89 heart transplan t recipients with soluble Mycobacterium tuberculosis extracts, a sourc e of heat shock proteins or recombinant mycobacterial heat shock prote in 65. T cell phenotypes were determined by flow cytometry. Results: M ycobacterium tuberculosis extract can induce lymphocyte propagation fr om heart transplant biopsy specimens especially during rejection. A hi ghly significant correlation was seen between Mycobacterium tuberculos is extract and interleukin-2-induced lymphocyte growth and an accelera ted growth was seen for cultures incubated with Mycobacterium tubercul osis extract + interleukin-2. A second series of experiments has also shown the propagation of lymphocytes induced by recombinant mycobacter ial heat shock protein-65. T-cell phenotype analysis of biopsy propaga ted lymphocytes has shown higher frequencies of CD8 cells in Mycobacte rium tuberculosis extract and heat shock protein-65 propagated lymphoc ytes from early posttransplantation biopsy specimens, whereas, later o n, most cultures showed a predominance of CD4 cells. T-cell receptor g ammadelta cells were more frequently found in biopsy-derived lymphocyt e cultures from long-term survivors, especially after propagation with Mycobacterium tuberculosis extract and heat shock protein-65. These g ammadelta cells expressed primarily the delta1 rather than the gamma9 phenotype.