In vitro T-Cell Responses as Surrogate Markers for HIV -lInfection Progression in Ethiopia

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Addis Ababa University


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