In vitro and In vivo Immune Responses in Ethiopian Tuberculosis Patients with HIV Infection
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Date
2001-06
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Addis Ababa University
Abstract
Mycobacteriulll tuberculosis and HIV - I arc known to interact with each other with an
impact on the immunological, virological/bacterial and clinical outcomes of both
infections. We aimed to evaluate the ill vitro and ill vivo immunolgical alterations in TB
and HlV-1 co-infection. The study population consisted of 101 subjects: HIV- and HlV+
individuals with TB (HlV-TB+, n=29; HIV+TB+, n=31), individuals with HIV only
(HlV+TB-, n=19), and healthy controls (HlV-TB-, n=22). Lymphoproliferative responses
were evaluated in mitogen- or antigen-stimulated PBMCs by BrdU ELISA. Cytokines
(IFN-y, IL-lO, and IL-12) in cell culturc supell1atants of PBMCs, and plasma
concentrations of TNF-a and TNF-RII werc measured by sandwich ELISA. Plasma viral
load was detelmined by nucleic acid sequence-based amplification; and C04+ T-cells
were enumerated by FACScan. Results showed that C04+ cell counts (cells/mm3) were
significantly reduced in individuals with TB and/or HlV infections compared to the
healthy controls. Patients co-infected with TB/HIV had a significantly elevated plasma
viral load (loglO copies/ml) as compared to HIV+ without TB. Proliferative responses
were reduced in TB+HlV- (1.36 and 0.58 to PHA and PPO, respectively), TB-HlV+ (1.17
and 0.40) as well as those with TB+HlV+ (1.13 and 0.47) compared to healthy controls
(1.76 and 0.83). IFN-y production was significantly depressed in TB+HIV- (P<O.OOI to
both PHA and PPO), TB-HlV+ (P=0.04, P=O.03 to PHA and PPO, respectively), and
TB+HlV+ (P=O.03, P=O.OI) when comparecito healthy controls. Although we did not see
statistically significant difference, there was a trend towards an increased JL..IO
production in response to PPO from TB+HIV- < TB-HlV+ < TB+HlV+. In comparison to
healthy controls, PPO-stimulated IL-12 levels were significantly reduced in the TB+HlV+
group (P=0.02). Plasma concentrations of TNF-a and sTNF-RII were progressively
v
increased from TB+HIV- (34.1 pg/ml and 7.8ng/ml, TNF-a and TNF-RII, respectively) <
TB-HIV+ (52.lpg/ml, 9.9ng/ml) < TB+HIV+ (63.5pg/ml, 15.lng/ml). There was a linear
positive correlation between sTNF-RII and viral load in TB-HIV+ group (R=O.75,
P=O.OI). Immunosuppression appeared to be protracted after three months of anti-TB
chemotherapy, and markers of immune activation remained elevated, in'espective of HIV
status. The data suggest that TB alYd HIV infections display partly similar and partly
distinct immune alterations, which may account for the exacerbation of disease outcomes
associated with both infections. The pattern of non-specific immune activation during
TBIHIV co-infection may be responsible for the enhanced replication of HIV-I and
accelerated disease progression.
VI
The tubercle bacillus preferentially infects macrophages and is noteworthy for having
evolved mechanisms that allow it to survive and mUltiply inside the phagocytic cell (Fine,
,~ 1994; Clemens, 1996). The cell envelope of the tubercle bacillus, exceptionally rich in the
unusual lipids, glycolipids and polysaccharides, may account for many of the unusual
characteristics of the bacillus, including ability to withstand the killing mechanisms of
macrophages and to replicate intracellularly, resist chemical and physical stresses, and be
impermeable to many antimicrobials and resist potent adjuvant activity, which may
contribute to the immunopathological manifestations of the disease (Kaufmann, 1993;
McKinney et al., 1998).
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Biology