AIDSWEEKLY Plus; Monday, December 13, 2004
Staff Medical Writers

"Human immunodeficiency virus (HIV) infection is characterized by a depletion of T cells. This depletion is caused both by the virus-induced death of infected T cells and by the death of uninfected cells (bystander depletion) by a mechanism which is largely uncharacterized.

"Regeneration and tolerance factor (RTF) is a subunit of the vacuolar ATPase and a protein that is involved with activation and apoptosis," researchers in the United States report.

"Anti-RTF antibodies mediate apoptosis in T lymphocytes. When anti-RTF was added to lymphocytes from an HIV-positive individual, they underwent larger amounts of apoptosis than cells taken from healthy controls.

"When lymphocytes were examined by Western blotting," R.A. Derks and colleagues wrote, "those from HIV-positive individuals exhibited increased levels of expression of the 50-kDa protein (P<0.001). A 70-kDa protein was the predominant form of RTF in uninfected control lymphocytes," the authors said, "being expressed in 100% of individuals studied."

"The expression of the 50-kDa protein in HIV-positive individuals correlated with decreased absolute CD4 counts with a sensitivity of 92% and a positive predictive value of 86%. When uninfected lymphocytes were stimulated with anti-CD3 and anti-CD28," continued scientists "no RTF was detected during early stimulation but a 50-kDa protein was expressed during late stimulation.

"When the susceptibilities of the lymphocytes to anti-RTF-induced apoptosis were measured, they correlated with the size of the RTF protein expressed. The cells were not susceptible to apoptosis when the 70-kDa RTF was present but were susceptible when the 50-kDa RTF was present."

Derks concluded, "We propose that the increase in the levels of the 50-kDa RTF on cells from HIV-positive individuals is important in preventing the cell from undergoing apoptosis."

Derks and colleagues published their study in Clinical and Diagnostic Laboratory Immunology (Regeneration and tolerance factor prevents bystander T-cell death associated with human immunodeficiency virus infection. Clin Diagn Lab Immunol. 2004 Sep;11(5):835-40.

For additional information, contact K.D. Beaman, Finch University Hlth Science Chicago Medical School, Department Microbiology & Immunology, 3333 Green Bay Rd., N Chicago, IL 60064, USA.

Publisher contact information for the journal Clinical and Diagnostic Laboratory Immunology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

The information in this article comes under the major subject areas of AIDS/HIV, Immunology, Proteomics and Apoptosis.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Derks RA, Beaman KD. "Regeneration and tolerance factor prevents bystander T-cell death associated with human immunodeficiency virus infection", Clin Diagn Lab Immunol. 2004 Sep;11(5):835-40.

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