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Journal of Virology, November 2004, p. 12638-12646, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12638-12646.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD4⁺ T Cells That Proliferate In Vitro Detected in Samples from Most Viremic Subjects and Inversely Associated with Plasma HIV-1 Levels

Eli Boritz,¹ Brent E. Palmer,² and Cara C. Wilson^1,2*

Departments of Immunology,¹ Medicine, University of Colorado Health Sciences Center, Denver, Colorado²

Received 31 March 2004/ Accepted 12 July 2004

Diminished in vitro proliferation of human immunodeficiency virus type 1 (HIV-1)-specific CD4⁺ T cells has been associated with HIV-1 viremia and declining CD4⁺ T-cell counts during chronic infection. To better understand this phenomenon, we examined whether HIV-1 Gag p24 antigen-induced CD4⁺ T-cell proliferation might recover in vitro in a group of subjects with chronic HIV-1 viremia and no history of antiretroviral therapy (ART). We found that depletion of CD8⁺ cells from peripheral blood mononuclear cells (PBMC) before antigen stimulation was associated with a 6.5-fold increase in the median p24-induced CD4⁺ T-cell proliferative response and a 57% increase in the number of subjects with positive responses. These p24-induced CD4⁺ T-cell proliferative responses from CD8-depleted PBMC were associated with expansion of the numbers of p24-specific, gamma interferon (IFN-)-producing CD4⁺ T cells. Among the 20 viremic, treatment-naïve subjects studied, the only 5 subjects lacking proliferation-competent, p24-specific CD4⁺ T-cell responses from CD8-depleted PBMC showed plasma HIV-1 RNA levels > 100,000 copies/ml. Furthermore, both the magnitude of p24-induced CD4⁺ T-cell proliferative responses from CD8-depleted PBMC and the frequency of p24-specific, IFN--producing CD4⁺ T cells expanded from CD8-depleted PBMC were associated inversely with plasma HIV-1 RNA levels. Therefore, proliferation-competent, HIV-1-specific CD4⁺ T cells that might help control HIV-1 disease may persist during chronic, progressive HIV-1 disease except at very high levels of in vivo HIV-1 replication.

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* Corresponding author. Mailing address: University of Colorado Health Sciences Center, Campus Box B-164, 4200 East 9th Ave., Denver, CO 80262. Phone: (303) 315-6659. Fax: (303) 315-7642. E-mail: Cara.Wilson{at}UCHSC.edu.

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Journal of Virology, November 2004, p. 12638-12646, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12638-12646.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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