Induction of "tissue" transglutaminase in HIV pathogenesis: Evidence for high rate of apoptosis of CD4+ T lymphocytes and accessory cells in lymphoid tissues

Alessandra Amendola, Marie Lise Gougeon, Fabrizio Poccia, Alain Bondurand, Laszlo Fesus, Mauro Piacentini

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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 ε(γ-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 ε(γ-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.

Original languageEnglish
Pages (from-to)11057-11062
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number20
DOIs
Publication statusPublished - Oct 1 1996

    Fingerprint

Keywords

  • AIDS
  • CD4 and CD8 T lymphocytes
  • Cell death
  • Follicular dendritic cells
  • Macrophages

ASJC Scopus subject areas

  • General

Cite this