Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy

Kenneth S Knox, Carol Vinton, Chadi A Hage, Lisa M Kohli, Homer L Twigg, Nichole R Klatt, Beth Zwickl, Jeffrey Waltz, Mitchell Goldman, Daniel C Douek, Jason M Brenchley

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The massive depletion of gastrointestinal-tract CD4 T cells is a hallmark of the acute phase of HIV infection. In contrast, the depletion of the lower-respiratory-tract mucosal CD4 T cells as measured in bronchoalveolar lavage (BAL) fluid is more moderate and similar to the depletion of CD4 T cells observed in peripheral blood (PB). To understand better the dynamics of disease pathogenesis and the potential for the reconstitution of CD4 T cells in the lung and PB following the administration of effective antiretroviral therapy, we studied cell-associated viral loads, CD4 T-cell frequencies, and phenotypic and functional profiles of antigen-specific CD4 T cells from BAL fluid and blood before and after the initiation of highly active antiretroviral therapy (HAART). The major findings to emerge were the following: (i) BAL CD4 T cells are not massively depleted or preferentially infected by HIV compared to levels for PB; (ii) BAL CD4 T cells reconstitute after the initiation of HAART, and their infection frequencies decrease; (iii) BAL CD4 T-cell reconstitution appears to occur via the local proliferation of resident BAL CD4 T cells rather than redistribution; and (iv) BAL CD4 T cells are more polyfunctional than CD4 T cells in blood, and their functional profile is relatively unchanged after the initiation of HAART. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might aid in the reconstitution of mucosal CD4 T cells.

Original languageEnglish (US)
Pages (from-to)9010-8
Number of pages9
JournalJournal of virology
Volume84
Issue number18
DOIs
StatePublished - Sep 2010

Keywords

  • Adult
  • Anti-HIV Agents/therapeutic use
  • Antiretroviral Therapy, Highly Active/methods
  • Blood/immunology
  • Bronchoalveolar Lavage Fluid/cytology
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes/immunology
  • Female
  • HIV Infections/drug therapy
  • Humans
  • Male
  • Middle Aged
  • Viral Load

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy'. Together they form a unique fingerprint.

  • Cite this

    Knox, K. S., Vinton, C., Hage, C. A., Kohli, L. M., Twigg, H. L., Klatt, N. R., Zwickl, B., Waltz, J., Goldman, M., Douek, D. C., & Brenchley, J. M. (2010). Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy. Journal of virology, 84(18), 9010-8. https://doi.org/10.1128/JVI.01138-10