Reconstitution of CD4 T cells in bronchoalveolar lavage fluid after initiation of highly active antiretroviral therapy.
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.
Knox
Kenneth S
KS
Southern Arizona VA Healthcare System and Arizona Respiratory Center and Division of Pulmonary and Critical Care Medicine, University of Arizona, Tucson, Arizona 85723, USA.
Vinton
Carol
C
Hage
Chadi A
CA
Kohli
Lisa M
LM
Twigg
Homer L
HL
Klatt
Nichole R
NR
Zwickl
Beth
B
Waltz
Jeffrey
J
Goldman
Mitchell
M
Douek
Daniel C
DC
Brenchley
Jason M
JM
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
D019380:Anti-HIV Agents