High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage.
The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to illuminate the pathogenesis of HIV-associated disease. Here, we studied depletion and HIV infection frequencies of CD4 T cells from the gastrointestinal tract, bronchoalveolar lavage (BAL), and blood with the frequencies and functional profiles of HIV-specific T cells in these anatomically distinct sites in HIV-infected individuals. The major findings to emerge were as follows: (i) depletion of gastrointestinal CD4 T cells is associated with high frequencies of infected CD4 T cells; (ii) HIV-specific T cells are present at low frequencies in the gastrointestinal tract compared to blood; (iii) BAL CD4 T cells are not massively depleted during the chronic phase; (iv) infection frequencies of BAL CD4 T cells are similar to those in blood; (v) significantly higher frequencies and increased functionality of HIV-specific T cells were observed in BAL compared to blood. Taken together, these data suggest mechanisms for mucosal CD4 T-cell depletion and interventions that might circumvent global depletion of mucosal CD4 T cells.
Brenchley
J M
JM
Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Knox
K S
KS
Asher
A I
AI
Price
D A
DA
Kohli
L M
LM
Gostick
E
E
Hill
B J
BJ
Hage
C A
CA
Brahmi
Z
Z
Khoruts
A
A
Twigg
H L
HL
Schacker
T W
TW
Douek
D C
DC
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005260:Female; D006678:HIV / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D009928:Organ Specificity / Q000276:immunology