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)9010-9018
Number of pages9
JournalJournal of virology
Volume84
Issue number18
DOIs
StatePublished - Sep 2010

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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), 9010-9018. https://doi.org/10.1128/JVI.01138-10