T cell apoptosis in human heart allografts - Association with lack of co-stimulation?

It is unclear whether the intracardial immune reactivity after heart transp lantation influences the peripheral immunological status (activation or non responsiveness) of the patient. Go-stimulation and activation-induced cell death (AICD) or apoptosis play an important role in determining the balance between lymphocyte reactivity and nonreactivity, Therefore, we studied the expression of co-stimulatory molecules and the process of apoptosis in bio psies of human heart allografts, using immunohistochemistry. Although a nor mal expression of costimulatory molecules on antigen-presenting cells was o bserved, the expression of their counter-structures on T cells was absent. This may be due to chronic T cell activation, which can lead to the inducti on of apoptosis via the Fas/Fas ligand pathway, In the infiltrates, a consi derable percentage of the lymphocytes, but not the macrophages, were apopto tic, Apoptosis was confirmed by DNA fragmentation analysis. Increased numbe rs of Bar-expressing versus decreased numbers of Bcl2-expressing lymphocyte s in comparison with normal lymphoid tissue confirmed a imbalance in favor of apoptosis, Apoptosis was biased towards CD4(+) T cells (65.7% versus 26. 6% in CD8(+) T cells). Fas was expressed on most of the infiltrating cells, Fas Ligand expression was also observed, not only on most of the T cells b ut also on all macrophages. Because macrophages were often detected in clos e contact with T cells, they may play a role In T cell regulation via the F as/Fas ligand pathway. This study indicates that, during rejection, not onl y is tissue damage induced by infiltrating T cells, but also the infiltrati ng lymphocytes themselves are actively down-regulated (eg, AICD) by one ano ther and by macrophages in the infiltrate, This regulatory process may affe ct the immunological status of the patient after heart transplantation.