INDUCTION OF TISSUE TRANSGLUTAMINASE IN HIV PATHOGENESIS - EVIDENCE FOR HIGH-RATE OF APOPTOSIS OF CD4(-LYMPHOCYTES AND ACCESSORY CELLS IN LYMPHOID-TISSUES() T)

Peripheral blood mononuclear cells and lymphoid tissues from HIV-infec ted individuals display high levels of ''tissue'' transglutaminase (tT G) with respect to seronegative persons. In asymptomatic individuals, >80% of the circulating CD4(+) T cells synthesize tTG protein and the number of these cells matches the level of apoptosis detected in the p eripheral blood mononuclear cells from the same patients. In HIV-infec ted lymph nodes tTG protein is localized in large number of cells (mac rophages, follicular dendritic cells, and endothelial cells), showing distinctive morphological and biochemical features of apoptosis as wel l as in lymphocytes and syncytia, These findings demonstrate that duri ng the course of HIV infection, high levels of apoptosis also occur in the accessory cells of lymphoid organs, The increased concentration o f epsilon(gamma-glutamyl)lysine isodipeptide, the degradation product of tTG cross-linked proteins, observed in the blood of HIV-infected in dividuals demonstrates that the enzyme accumulated in the dying cells actively cross-links intracellular proteins, The enhanced levels of ep silon(gamma-glutamyl)lysine in the blood parallels the progression of HIV disease, suggesting that the isodipeptide determination might be a useful method to monitor the in vivo rate of apoptosis.