Failure of T-cell homeostasis preceding AIDS in HIV-1 infection

Joseph Bernard Margolick, Alvaro Munoz, Albert D. Donnenberg, Lawrence P. Park, Noya Galai, Janis V. Giorgi, Maurice R G O'Gorman, John Ferbas, Alfred J. Saah, Haroutune Armenian, Homayoon Farzadegan, Neil Graham, Nancy Kass, Joseph Margolick, Justin McArthur, Ellen Taylor, John P. Phair, Joan S. Chmiel, Bruce Cohen, Maurice O'GormanDaina Variakojis, Jerry Wesch, Steven M. Wolinsky, Roger Detels, Barbara R. Visscher, Irvin S Y Chen, Janice Dudley, John L. Fahey, Moon Lee, Oto Martinez-Maza, Eric N. Miller, Parunag Nishanian, Jeremy Taylor, Jerome Zack, Charles R. Rinaldo, Lawrence Kingsley, James T. Becker, Phalguni Gupta, Monto Ho, Sharon Zucconi, Leonardo Epstein, Stephen Gange, Donald R. Hoover, Lisa P. Jacobson, Kenrad Nelson, Steven Piantadosi, Sol Su, Lewis Schrager, Daniela Seminara

Research output: Contribution to journalArticle

Abstract

We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T- cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident human immunodeficiency virus, type 1 (HIV-1), infection who remained free of acquired immunodeficiency syndrome (AIDS) for up to eight years after seroconversion. In contrast, seroconverters who developed AIDS exhibited rapidly declining T cells (both CD4+ and CD8+) for approximately two years before AIDS, independent of the time between seroconversion and AIDS, suggesting that homeostasis failure is an important landmark in HIV disease progression. Given the high rate of T-cell turnover in HIV-1 infection, blind T-cell homeostasis may contribute to HIV pathogenesis through a CD8+ T lymphocytosis that interferes with regeneration of lost CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)674-680
Number of pages7
JournalNature Medicine
Volume1
Issue number7
DOIs
StatePublished - 1995

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T-cells
Virus Diseases
Viruses
HIV-1
Acquired Immunodeficiency Syndrome
Homeostasis
T-Lymphocytes
Theophylline
HIV
Lymphocytosis
Disease Progression
Regeneration
Phenotype

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. / Margolick, Joseph Bernard; Munoz, Alvaro; Donnenberg, Albert D.; Park, Lawrence P.; Galai, Noya; Giorgi, Janis V.; O'Gorman, Maurice R G; Ferbas, John; Saah, Alfred J.; Armenian, Haroutune; Farzadegan, Homayoon; Graham, Neil; Kass, Nancy; Margolick, Joseph; McArthur, Justin; Taylor, Ellen; Phair, John P.; Chmiel, Joan S.; Cohen, Bruce; O'Gorman, Maurice; Variakojis, Daina; Wesch, Jerry; Wolinsky, Steven M.; Detels, Roger; Visscher, Barbara R.; Chen, Irvin S Y; Dudley, Janice; Fahey, John L.; Lee, Moon; Martinez-Maza, Oto; Miller, Eric N.; Nishanian, Parunag; Taylor, Jeremy; Zack, Jerome; Rinaldo, Charles R.; Kingsley, Lawrence; Becker, James T.; Gupta, Phalguni; Ho, Monto; Zucconi, Sharon; Epstein, Leonardo; Gange, Stephen; Hoover, Donald R.; Jacobson, Lisa P.; Nelson, Kenrad; Piantadosi, Steven; Su, Sol; Schrager, Lewis; Seminara, Daniela.

In: Nature Medicine, Vol. 1, No. 7, 1995, p. 674-680.

Research output: Contribution to journalArticle

Margolick, JB, Munoz, A, Donnenberg, AD, Park, LP, Galai, N, Giorgi, JV, O'Gorman, MRG, Ferbas, J, Saah, AJ, Armenian, H, Farzadegan, H, Graham, N, Kass, N, Margolick, J, McArthur, J, Taylor, E, Phair, JP, Chmiel, JS, Cohen, B, O'Gorman, M, Variakojis, D, Wesch, J, Wolinsky, SM, Detels, R, Visscher, BR, Chen, ISY, Dudley, J, Fahey, JL, Lee, M, Martinez-Maza, O, Miller, EN, Nishanian, P, Taylor, J, Zack, J, Rinaldo, CR, Kingsley, L, Becker, JT, Gupta, P, Ho, M, Zucconi, S, Epstein, L, Gange, S, Hoover, DR, Jacobson, LP, Nelson, K, Piantadosi, S, Su, S, Schrager, L & Seminara, D 1995, 'Failure of T-cell homeostasis preceding AIDS in HIV-1 infection', Nature Medicine, vol. 1, no. 7, pp. 674-680. https://doi.org/10.1038/nm0795-674
Margolick, Joseph Bernard ; Munoz, Alvaro ; Donnenberg, Albert D. ; Park, Lawrence P. ; Galai, Noya ; Giorgi, Janis V. ; O'Gorman, Maurice R G ; Ferbas, John ; Saah, Alfred J. ; Armenian, Haroutune ; Farzadegan, Homayoon ; Graham, Neil ; Kass, Nancy ; Margolick, Joseph ; McArthur, Justin ; Taylor, Ellen ; Phair, John P. ; Chmiel, Joan S. ; Cohen, Bruce ; O'Gorman, Maurice ; Variakojis, Daina ; Wesch, Jerry ; Wolinsky, Steven M. ; Detels, Roger ; Visscher, Barbara R. ; Chen, Irvin S Y ; Dudley, Janice ; Fahey, John L. ; Lee, Moon ; Martinez-Maza, Oto ; Miller, Eric N. ; Nishanian, Parunag ; Taylor, Jeremy ; Zack, Jerome ; Rinaldo, Charles R. ; Kingsley, Lawrence ; Becker, James T. ; Gupta, Phalguni ; Ho, Monto ; Zucconi, Sharon ; Epstein, Leonardo ; Gange, Stephen ; Hoover, Donald R. ; Jacobson, Lisa P. ; Nelson, Kenrad ; Piantadosi, Steven ; Su, Sol ; Schrager, Lewis ; Seminara, Daniela. / Failure of T-cell homeostasis preceding AIDS in HIV-1 infection. In: Nature Medicine. 1995 ; Vol. 1, No. 7. pp. 674-680.
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AU - O'Gorman, Maurice R G

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AU - Saah, Alfred J.

AU - Armenian, Haroutune

AU - Farzadegan, Homayoon

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AU - Kass, Nancy

AU - Margolick, Joseph

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AU - Taylor, Ellen

AU - Phair, John P.

AU - Chmiel, Joan S.

AU - Cohen, Bruce

AU - O'Gorman, Maurice

AU - Variakojis, Daina

AU - Wesch, Jerry

AU - Wolinsky, Steven M.

AU - Detels, Roger

AU - Visscher, Barbara R.

AU - Chen, Irvin S Y

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AU - Nishanian, Parunag

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AU - Becker, James T.

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AU - Epstein, Leonardo

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