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Regeneration and tolerance factor prevents bystander T-cell death associated with human immunodeficiency virus infection.

Abstract
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. 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, 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, 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, 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. 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.
AuthorsRichard A Derks, Kenneth D Beaman
JournalClinical and diagnostic laboratory immunology (Clin Diagn Lab Immunol) Vol. 11 Issue 5 Pg. 835-40 (Sep 2004) ISSN: 1071-412X [Print] United States
PMID15358640 (Publication Type: Journal Article)
Chemical References
  • Suppressor Factors, Immunologic
  • regeneration and tolerance factor
  • Adenosine Triphosphate
  • Vacuolar Proton-Translocating ATPases
Topics
  • Adenosine Triphosphate (pharmacology)
  • Apoptosis
  • Bystander Effect
  • CD4-Positive T-Lymphocytes (chemistry, pathology, virology)
  • Case-Control Studies
  • HIV Infections (immunology, pathology)
  • Humans
  • Molecular Weight
  • Suppressor Factors, Immunologic (analysis, physiology)
  • T-Lymphocytes (chemistry, pathology, virology)
  • Vacuolar Proton-Translocating ATPases (metabolism)

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