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Clinical and Diagnostic Laboratory Immunology, September 2004, p. 835-840, Vol. 11, No. 5
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.5.835-840.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Regeneration and Tolerance Factor Prevents Bystander T-Cell Death Associated with Human Immunodeficiency Virus Infection

Richard A. Derks and Kenneth D. Beaman*

Department of Microbiology and Immunology, Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois

Received 4 December 2003/ Returned for modification 6 February 2004/ Accepted 14 May 2004

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.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, Finch University of Health Sciences/The Chicago Medical School, 3333 Green Bay Rd., North Chicago, IL 60064. Phone: (847) 578-3449. Fax: (847) 775-6506. E-mail: kbeaman{at}aol.com.

Clinical and Diagnostic Laboratory Immunology, September 2004, p. 835-840, Vol. 11, No. 5
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.5.835-840.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





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