title: Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy.
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.
authors.affiliation: Southern Arizona VA Healthcare System and Arizona Respiratory Center and Division of Pulmonary and Critical Care Medicine, University of Arizona, Tucson, Arizona 85723, USA.
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Knox
authors.forename: Carol
authors.initials: C
authors.lastname: Vinton
authors.forename: Chadi A
authors.initials: CA
authors.lastname: Hage
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kohli
authors.forename: Homer L
authors.initials: HL
authors.lastname: Twigg
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
authors.forename: Beth
authors.initials: B
authors.lastname: Zwickl
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Waltz
authors.forename: Mitchell
authors.initials: M
authors.lastname: Goldman
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.forename: Jason M
authors.initials: JM
authors.lastname: Brenchley
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D001769:Blood / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents