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Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes

Nature Medicine volume 1, pages 129–134 (1995)Cite this article

Abstract

Although 13 years have passed since identification of human immunodeficiency virus-1 (HIV-1) as the cause of AIDS, we do not yet know how HIV kills its primary target, the T cell that carries the CD4 antigen. We and others have shown an increase in the percentage of apoptotic cells among circulating CD4+ (and CD8+) T cells of HIV-seropositive individuals and an increase in frequency of apoptosis with disease progression. However, it is not known if this apoptosis occurs in infected or uninfected T cells. We show here, using in situ labelling of lymph nodes from HIV-infected children and SIV-infected macaques, that apoptosis occurs predominantly in bystander cells and not in the productively infected cells themselves. These data have implications for pathogenesis and therapy, namely, arguing that rational drug therapy may involve combination agents targeting viral replication in infected cells and apoptosis of uninfected cells.

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Author notes

  1. T. H. Finkel: Correspondence should be addressed to T.H.F.

Authors and Affiliations

  1. Department of Pediatrics, Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, 1400 Jackson Street, Denver, Colorado, 80206, USA

    T. H. Finkel, N. K. Banda, C. Monks & A. Kupfer

  2. Department of Pediatrics, Immunology, and Biochemistry, Biophysics and Genetics, 4200 East Ninth Avenue, Denver, Colorado, 80262, USA

    T. H. Finkel

  3. Department of Infectious Diseases, 4200 East Ninth Avenue, Denver, Colorado, 80262, USA

    M. F. Cotton & T. Curiel

  4. Department of Cell and Structural Biology and Immunology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado, 80262, USA

    C. Monks & A. Kupfer

  5. Pediatric Branch, National Cancer Institute, 9000 Rockville Pike, Building 10, Bethesda, Maryland, 20892, USA

    G. Tudor-Williams

  6. Laboratory of Viral Pathogenesis, Dana–Farber Cancer Institute, and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, Massachusetts, 02115, USA

    T. W. Baba & R. M. Ruprecht

  7. Department of Pediatrics, Division of Newborn Medicine, Tufts University School of Medicine, 750 Washington Street, Boston, Massachusetts, 02111, USA

    T. W. Baba

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  1. T. H. Finkel
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  9. A. Kupfer
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Finkel, T., Tudor-Williams, G., Banda, N. et al. Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes. Nat Med 1, 129–134 (1995). https://doi.org/10.1038/nm0295-129

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