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

19 Citations (Scopus)

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 - 2010

Fingerprint

Highly Active Antiretroviral Therapy
Bronchoalveolar Lavage Fluid
T-lymphocytes
T-Lymphocytes
therapeutics
Bronchoalveolar Lavage
blood
fluids
CD4 Antigens
HIV infections
Cell- and Tissue-Based Therapy
viral load
Viral Load
respiratory system
Respiratory System
HIV Infections
gastrointestinal system
Gastrointestinal Tract
pathogenesis

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

Cite this

Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy. / Knox, Kenneth S; Vinton, Carol; Hage, Chadi A.; Kohli, Lisa M.; Twigg, Homer L.; Klatt, Nichole R.; Zwickl, Beth; Waltz, Jeffrey; Goldman, Mitchell; Douek, Daniel C.; Brenchley, Jason M.

In: Journal of Virology, Vol. 84, No. 18, 2010, p. 9010-9018.

Research output: Contribution to journalArticle

Knox, KS, Vinton, C, Hage, CA, Kohli, LM, Twigg, HL, Klatt, NR, Zwickl, B, Waltz, J, Goldman, M, Douek, DC & Brenchley, JM 2010, 'Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy', Journal of Virology, vol. 84, no. 18, pp. 9010-9018. https://doi.org/10.1128/JVI.01138-10
Knox, Kenneth S ; Vinton, Carol ; Hage, Chadi A. ; Kohli, Lisa M. ; Twigg, Homer L. ; Klatt, Nichole R. ; Zwickl, Beth ; Waltz, Jeffrey ; Goldman, Mitchell ; Douek, Daniel C. ; Brenchley, Jason M. / Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy. In: Journal of Virology. 2010 ; Vol. 84, No. 18. pp. 9010-9018.
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