Induction of ``Tissue" Transglutaminase in HIV Pathogenesis: Evidence for High Rate of Apoptosis of CD4$^{+}$ T Lymphocytes and Accessory Cells in Lymphoid Tissues

Peripheral blood mononuclear cells and lymphoid tissues from HIV-infected individuals display high levels of ``tissue'' transglutaminase (tTG) with respect to seronegative persons. In asymptomatic individuals, >80% of the circulating CD4$^{+}$ T cells synthesize tTG protein and the numb...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-10, Vol.93 (20), p.11057-11062
Main Authors: Amendola, Alessandra, Gougeon, Marie-Lise, Poccia, Fabrizio, Bondurand, Alain, Fesus, Laszlo, Piacentini, Mauro
Format: Article
Language:English
Subjects:
AIDS
AIDS/HIV
Antibodies
Apoptosis
B lymphocytes
Blood
CD4-Positive T-Lymphocytes - enzymology
Dipeptides - blood
DNA Fragmentation
Enzymes
Follicular dendritic cells
GTP Phosphohydrolases - metabolism
GTP-Binding Proteins
HIV Infections - enzymology
HIV Infections - pathology
HIV-1
HIV-2
Humans
Immunophenotyping
Lymph nodes
Lymphoid tissue
Lymphoid Tissue - enzymology
T lymphocytes
Transglutaminases - metabolism
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Summary:Peripheral blood mononuclear cells and lymphoid tissues from HIV-infected individuals display high levels of ``tissue'' transglutaminase (tTG) 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 peripheral blood mononuclear cells from the same patients. In HIV-infected lymph nodes tTG protein is localized in large number of cells (macrophages, follicular dendritic cells, and endothelial cells), showing distinctive morphological and biochemical features of apoptosis as well as in lymphocytes and syncytia. These findings demonstrate that during the course of HIV infection, high levels of apoptosis also occur in the accessory cells of lymphoid organs. The increased concentration of $\varepsilon $($\gamma $-glutamyl)lysine isodipeptide, the degradation product of tTG cross-linked proteins, observed in the blood of HIV-infected individuals demonstrates that the enzyme accumulated in the dying cells actively cross-links intracellular proteins. The enhanced levels of $\varepsilon $($\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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.20.11057