In vitro T-Cell Responses as Surrogate Markers for HIV -lInfection Progression in Ethiopia
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Date
2000-06
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Addis Ababa University
Abstract
In an effort to use immunological abnormalities as markers of HI V -I infection
progression in Ethiopian individuals, this work assessed the changes in in vitro and in
vivo T-cell responses to recall M. tuberculosis antigen, purified protein derivative
(PPO). This was further evaluated against C04+ and C08+ T-cells count and viral load
in the same subjects. Peripheral blood mononuclear cells (PBMCs) isolated from 36
HIV -I seropositive and 105 seronegative individuals were subjected to 6 days in vitro
PPO stimulation and cytokine production. The T-cell proliferative response was then
evaluated using 5-bromo-2-deoxyuridine (BrdU) instead of thymidine incorporation as
a method of assay. Cytokines (IFN-y and IL-4) production was measured in the PBMC
culture supernatants using sandwich ELISA. Three days phytoheamagglutinin (PHA)
stimulation responses were used as positive controls. In vivo tuberculin PPO responses
were measured for 18 HIV -I seropositive and 74 seronegative individuals by standard
Mantoux reaction. Results show that T-cell responses to PPO both in vitro and in vivo
were affected by HIV -I infection, in contrast to HIV -I seronegatives. Significant
reduction in IFN-y production was also observed between the two groups following
PPO stimulation (p = 0.000), but not with IL-4. Thus, a shift from Thl to Th2
cytokines production was not observed. Analysis of T --;;ell responses to PPO showed a
positive correlation with C04+ T cell counts, and negative with plasma viral load. This
confirmed that HIV -I infection progression is followed by a depletion of C04+ T cells
count and high viral load. Change in proliferation and cytokine production was specific
to PPO. It suggests that Alycobacteriulll tuberculosis specific immune responses are
affected in HIV -I infected sUbjects. Taken together our results indicated that evaluating
T-cell responses to recall antigen, PPO can be used as an early marker for HIV -I
infection progression.of unemployment, sexual promiscuity and the presence of a wide diversity of HIV-I
subtypes in Africa have also been indicated as powerful components in HIV -I spread and
transmission.
The virus has profound economic and social implications for both developed and
developing countries. No country in the world is free of the disease and can claim that it
has stopped its spread. The most effective and efficient method to prevent HIV -infection
and disease manifestation would be through vaccination and effective treatment, which
currently are not available. The generally accepted method of implementing preventive
strategies for HIV infection is education that will inform and increase awareness of the
society
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Biology