Early depletion of Mycobacterium tuberculosis-specific T helper 1 cell responses after HIV-1 infection.
BACKGROUND
The acid-fast bacillus Mycobacterium tuberculosis is often the first manifestation of acquired immunodeficiency syndrome in patients infected with human immunodeficiency virus (HIV). This study was conducted to better understand the mechanism underlying M. tuberculosis-specific pathogenicity early after onset of HIV infection.


METHODS
M. tuberculosis-specific T helper 1 (Th1) cells were studied in HIV negative (n=114) and chronically HIV infected (n=68) Tanzanian subjects by using early secreted antigenic target 6 (ESAT6) protein or tuberculin (purified protein derivative) with interferon-gamma ELISPOT and intracellular cytokine staining. In a longitudinal study, the effect of acute HIV infection on M. tuberculosis-specific Th1 cells was determined by polychromatic flow cytometric analysis in 5 subjects with latent M. tuberculosis infection who became infected with HIV.


RESULTS
In tuberculosis (TB)-asymptomatic subjects (i.e., subjects with unknown TB status who did not show clinical signs suggestive of TB), chronic HIV infection was associated with a decreased percentage of subjects with detectable M. tuberculosis-specific Th1 cells (P< .001) a decrease which was not observed among subjects with active TB. Acute HIV infection induced a rapid depletion of M. tuberculosis-specific Th1 cells in 4 subjects remained TB asymptomatic, whereas the population of these cells remained stable in subjects who remained HIV negative (P< .01).


CONCLUSIONS
Taken together, these data suggest a mechanism of rapid M. tuberculosis-specific Th1 cell depletion that may contribute to the early onset of TB in individuals with latent M. tuberculosis infection who become HIV infected.
Geldmacher
Christof
C
Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. geldmacher@lrz.uni-muenchen.de
Schuetz
Alexandra
A
Ngwenyama
Njabulo
N
Casazza
Joseph P
JP
Sanga
Erica
E
Saathoff
Elmar
E
Boehme
Catharina
C
Geis
Steffen
S
Maboko
Leonard
L
Singh
Mahavir
M
Minja
Fred
F
Meyerhans
Andreas
A
Koup
Richard A
RA
Hoelscher
Michael
M
D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes; D003430:Cross-Sectional Studies; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000150:complications / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D019713:Receptors, CCR5