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The CD28/HLA-DR expressions on CD4+T but not CD8+T cells are significant predictors for progression to AIDS
Byeong-Sun Choi1, Yong-Keun Park, Joo-Shil Lee
1Centre for AIDS Research, Department of Virology, National Institute of Health, Seoul, Korea.
Insights
Changes in CD28 and HLA-DR molecules on T cells during HIV infection reveal distinct patterns. CD4+ T cell molecule expression changes predict disease progression, unlike CD8+ T cells.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- HIV infection significantly impacts T cell populations, crucial for immune response.
- CD28 and HLA-DR are key molecules on T cells involved in immune regulation and activation.
- Understanding T cell marker dynamics is vital for monitoring HIV disease progression.
Purpose of the Study:
- To investigate the expression patterns of CD28 and HLA-DR on CD4+ and CD8+ T cells in HIV-infected individuals.
- To correlate these molecular changes with CD4+ T cell counts and disease stages.
- To assess the predictive value of these markers for HIV disease progression.
Main Methods:
- Categorization of 130 HIV-infected Koreans into four groups based on CD4+ T cell counts.
- Flow cytometry analysis to quantify CD28 and HLA-DR expression on CD4+ and CD8+ T cells.
- Statistical analysis to compare marker expression across different disease stages.
Main Results:
- CD4+ T cells showed decreased CD28 and increased HLA-DR expression correlating with lower CD4+ counts.
- CD8+ T cells exhibited rapid CD28 down-regulation early in HIV infection, with stable expression thereafter.
- The combined expression of CD28 and HLA-DR on both T cell types remained relatively constant (~100% and ~55-60%).
Conclusions:
- CD4+ T cell CD28/HLA-DR expression changes are more indicative of HIV disease progression than those on CD8+ T cells.
- CD8+ T cell CD28 down-regulation, despite severity, may not impact survival in this cohort.
- Further research is needed to elucidate the constant sum of CD28 and HLA-DR expression in T cells.
Abstract:
To investigate the changes of CD28 and HLA-DR molecules on CD4+ and CD8+ T cells during HIV infection, we classified 130 HIV-infected Koreans into four groups by the CD4 level as follows: group I (> or = 500 cells/mm3), group II (201-499 cells/mm3), group III (51-200 cells/mm3), and group IV (< or = 50 cells/mm3). In CD4+ T cells, the proportion of CD28 expression decreased significantly with the CD4 level while the proportion of HLA-DR expression increased gradually. In particular, the changes of HLA-DR expressions on CD4+ T cells were parallel to the loss of CD28 molecules from stage III to IV. However, the CD28 expression on CD8+ T cells decreased dramatically in the early stage of HIV infection, and the sum and pattern of CD28 and HLA-DR expressions on CD8+ T cells was stable after the first stage. Even though CD28 down-regulation on CD8+ T cells was very severe from the early stage of HIV infection, it might not influence the survival time of HIV-infected Koreans. The sum of the CD28+ subsets and HLA-DR subsets in each T cell was stable in all stages of disease progression. The sums of the CD28+ subsets and HLA-DR+ subsets in CD4+ T and CD8+ T cells were constant as approximately 100% and 55-60% of each T cell. These results suggested that the changes of CD28/HLA-DR expressions on CD4+ T cells were more predictable than those on CD8+ T cells in the evaluation of the disease progression during HIV-infected periods. However, we need further studies to understand why the sum of two molecules in each T cell are constant.
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