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Clinical and Diagnostic Laboratory Immunology, November 1999, p. 872-877, Vol. 6, No. 6
1071-412X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Regeneration and Tolerance Factor: a Correlate of Human Immunodeficiency Virus-Associated T-Cell Activation

Tara S. Givens,1 Brian K. DuChateau,1 Jonathan S. Boomer,1 Maxwell P. Westerman,2 Alice Gilman-Sachs,1 and Kenneth D. Beaman1,*

Clinical Immunology Laboratory and Department of Microbiology/Immunology, Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois 60064,1 and Department of Medicine, Mount Sinai Hospital, Chicago, Illinois 606082

Received 14 April 1999/Returned for modification 24 June 1999/Accepted 25 August 1999

Human immunodeficiency virus (HIV) infection causes extensive phenotypic alterations in lymphocytes. Cellular markers that are normally absent or expressed at low levels on quiescent cells are upregulated throughout the disease course. The transmembrane form of regeneration and tolerance factor (RTF) is expressed at negligible levels on resting T cells but is quickly upregulated following in vitro stimulation and activation. Recently, we reported that expression of RTF was significantly higher in cells from HIV-seropositive (HIV+) individuals than in cells from HIV-seronegative (HIV-) individuals. Because T cells from HIV+ individuals express markers reflecting chronic activation, we hypothesized that these in vivo-activated cells would coexpress RTF. Flow cytometry was used to assess RTF expression on activated (CD38+ and HLA-DR+) CD4+ and CD8+ T cells. HIV+ individuals had higher percentages of RTF+ CD38+ (P < 0.0001) or RTF+ HLA-DR+ (P = 0.0001) CD4+ T cells than HIV- individuals. In HIV+ individuals, increased percentages of CD4+ T cells that were RTF+, RTF+ CD38+, and RTF+ HLA-DR+ correlated inversely with the absolute number and percentage of CD4+ T cells and correlated positively with plasma beta 2-microglobulin concentrations. HIV+ individuals had higher percentages of CD8+ T cells that were RTF+ CD38+ (P = 0.0001) or RTF+ HLA-DR+ (P = 0.0010). In HIV+ individuals, increased percentages of CD8+ T cells that were RTF+ HLA-DR+ correlated inversely with the percentage of CD4+ T cells, and high percentages of CD8+ T cells that were RTF+ CD38+ correlated positively with plasma beta 2-microglobulin levels. These findings strongly suggest that increased RTF expression is a correlate of HIV-associated immune system activation.

* Corresponding author. Mailing address: FUHS/The Chicago Medical School, Clinical Immunology Laboratory, 3333 Green Bay Rd., North Chicago, IL 60064. Phone: (847) 578-3449. Fax: (874) 578-3349. E-mail: kbeaman{at}aol.com.

Clinical and Diagnostic Laboratory Immunology, November 1999, p. 872-877, Vol. 6, No. 6
1071-412X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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