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Increased production of IL-7 accompanies HIV-1–mediated T-cell depletion: implications for T-cell homeostasis

Nature Medicine volume 7, pages 73–79 (2001)Cite this article

Abstract

We hypothesized that HIV-1–mediated T-cell loss might induce the production of factors that are capable of stimulating lymphocyte development and expansion. Here we perform cross-sectional (n = 168) and longitudinal (n = 11) analyses showing that increased circulating levels of interleukin (IL)-7 are strongly associated with CD4+ T lymphopenia in HIV-1 disease. Using immunohistochemistry with quantitative image analysis, we demonstrate that IL-7 is produced by dendritic-like cells within peripheral lymphoid tissues and that IL-7 production by these cells is greatly increased in lymphocyte-depleted tissues. We propose that IL-7 production increases as part of a homeostatic response to T-cell depletion.

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Figure 1: Changes in IL-7, CD4+ T cell count, and viral load over the course of HIV-1 disease progression.
Figure 2: Longitudinal analysis showing changes in 11 subjects followed for 6–25 mo.
Figure 3: Production of IL-7 within peripheral lymphoid tissue.

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Acknowledgements

We thank the study participants, Project Inform and other AIDS community members for support; L. Radler, R. Halvorsen, R. Loftus, S. Lee, M. Weinstein, M.B. Hanley and K. Bastani for technical contributions; N. Abbey, B. Hoh, E. Duecy, M. Thounaojam, P. Wong and J. Javier for assistance; T. Fry and C. Mackall for unpublished observations; and B. Bredt and other members of the UCSF/Macy's Center for Creative Therapies and the Core Immunology Laboratory, as well as the San Francisco General Hospital General Clinical Research Center, for specimen processing and analysis. L.A.N and R.M.G were supported by the J. David Gladstone Institutes. L.A.N was supported by the NIH (AI01597). S.C.D. was supported by the University of California University-wide AIDS Research Program (F97-ST-044) and the NIH (CA42059). R.M.G and B.H. were supported by the UCSF Center for AIDS Research (P30 MH59037) and B.H. was also supported by the NIH (CA66529). J.A. was supported by grants from the Medical Research Council (10850) and by the NIH (AI41536). J.M.M. was supported by the Elizabeth Glaser Pediatric AIDS Foundation and by grants from the NIH (AI43864, AI47062, and AI40312) . The SFGH GCRC was supported by an NIH Grant from the Division of Research Resources.

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Authors and Affiliations

  1. Gladstone Institute of Virology and Immunology, San Francisco General Hospital, University of California at San Francisco, San Francisco, 94110-9100, California, USA

    Laura A. Napolitano, Robert M. Grant, Diane Schmidt & Joseph M. McCune

  2. Department of Medicine, University of California at San Francisco, San Francisco, 94110-9100, California, USA

    Laura A. Napolitano, Robert M. Grant, Steven G. Deeks & Joseph M. McCune

  3. Department of Pathology, University of California at San Francisco, San Francisco, 94110-9100, California, USA

    Brian G. Herndier

  4. Department of Microbiology and Immunology, University of California at San Francisco, San Francisco, 94110-9100, California, USA

    Joseph M. McCune

  5. Department of Genetics Stanford University, Palo Alto, 94305, California, USA

    Stephen C. De Rosa & Leonore A. Herzenberg

  6. Department of Infectious Diseases, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden

    Jan Andersson

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Correspondence to Joseph M. McCune.

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Napolitano, L., Grant, R., Deeks, S. et al. Increased production of IL-7 accompanies HIV-1–mediated T-cell depletion: implications for T-cell homeostasis. Nat Med 7, 73–79 (2001). https://doi.org/10.1038/83381

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