Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression

Scott Koenig; Anthony J. Conley; Yambasu A. Brewah; Gary M. Jones; Simon Leath; Lynn J. Boots; Victoria Davey; Guiseppi Pantaleo; James F. Demarest; Charles Carter; Christine Wannebo; John R. Yannelli; Steven A. Rosenberg; H. Clifford Lane

doi:10.1038/nm0495-330

Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression

Scott Koenig, Anthony J. Conley, Yambasu A. Brewah, Gary M. Jones, Simon Leath, Lynn J. Boots, Victoria Davey, Guiseppi Pantaleo, James F. Demarest, Charles Carter, Christine Wannebo, John R. Yannelli, Steven A. Rosenberg, H. Clifford Lane

Research output: Contribution to journal › Article › peer-review

341 Scopus citations

Abstract

An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 net protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4⁺T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4⁺cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.

Original language	English
Pages (from-to)	330-336
Number of pages	7
Journal	Nature Medicine
Volume	1
Issue number	4
DOIs	https://doi.org/10.1038/nm0495-330
State	Published - Apr 1995

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nm0495-330

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Koenig, S., Conley, A. J., Brewah, Y. A., Jones, G. M., Leath, S., Boots, L. J., Davey, V., Pantaleo, G., Demarest, J. F., Carter, C., Wannebo, C., Yannelli, J. R., Rosenberg, S. A., & Lane, H. C. (1995). Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nature Medicine, 1(4), 330-336. https://doi.org/10.1038/nm0495-330

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abstract = "An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 net protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.",

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Koenig, S, Conley, AJ, Brewah, YA, Jones, GM, Leath, S, Boots, LJ, Davey, V, Pantaleo, G, Demarest, JF, Carter, C, Wannebo, C, Yannelli, JR, Rosenberg, SA & Lane, HC 1995, 'Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression', Nature Medicine, vol. 1, no. 4, pp. 330-336. https://doi.org/10.1038/nm0495-330

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AU - Koenig, Scott

AU - Conley, Anthony J.

AU - Brewah, Yambasu A.

AU - Jones, Gary M.

AU - Leath, Simon

AU - Boots, Lynn J.

AU - Davey, Victoria

AU - Pantaleo, Guiseppi

AU - Demarest, James F.

AU - Carter, Charles

AU - Wannebo, Christine

AU - Yannelli, John R.

AU - Rosenberg, Steven A.

AU - Lane, H. Clifford

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N2 - An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 net protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.

AB - An HIV-1-seropositive volunteer was infused with an expanded autologous cytotoxic T lymphocyte (CTL) clone directed against the HIV-1 net protein. This clone was adoptively transferred to determine whether supplementing CTL activity could reduce viral load or improve clinical course. Unexpectedly, infusion was followed by a decline in circulating CD4+T cells and a rise in viral load. Some of the HIV isolates obtained from the plasma or CD4+cells of the patient were lacking the nef epitope. These results suggest that active CTL selection of viral variants could contribute to the pathogenesis of AIDS and that clinical progression can occur despite high levels of circulating HIV-1-specific CTLs.

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Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression

Abstract

ASJC Scopus subject areas

UN SDGs

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