Decreased CD4+CD8low T cells in early HIV infection are associated with rapid disease progression

Abstract

Background: HIV rapid progressors (RPs) present with a rapid decline of CD4⁺ T cells within a few years of infection. Determining the underlying mechanisms throughout this decline is important to identify prognostic biomarkers and intervention strategies. Determining the numbers of CD4⁺ and CD8⁺ T cells is essential for monitoring the immune status of HIV infected patients. There are additional kinds of cell subtypes in T cells, but their relationship to the rapid progression of HIV disease is not well defined.

Methods: Nineteen RPs and twenty-one chronic progressors (CPs) were enrolled in this study. Based on the intensity of CD4 and CD8 expression, different T cell subtypes were identified, including CD4⁺CD8⁺T cells, CD4^-CD8^- T cells, CD4⁺CD8^low T cells and CD4^-CD8^low T cells. Alterations in these T cell subtypes in early HIV infection (within 120 days of infection) between RPs and CPs were measured, and the relationships between these subtypes and HIV disease progression were investigated. In addition, expression of IFN-γ in T cell subtypes after PMA stimulation was analyzed by flow cytometry.

Results: We found that during early HIV infection, CD4⁺CD8^low T cells both significantly decreased in numbers and percentages in RPs compared to CPs. Furthermore, baseline CD4⁺CD8^low T cells positively correlated not only with baseline CD4⁺T cells but also with CD4⁺T cells 12 months after infection. Moreover, survival analysis indicated that low levels of baseline CD4⁺CD8low T cells significantly accelerated the decline in CD4⁺ T cells as well as increased viral loads. CD4⁺CD8^low T cells secreted significantly more IFN-γ after PMA stimulation compared to CD4⁺CD8^-T cells and CD4^-CD8⁺T cells, which may be beneficial for the prevention of disease progression.

Conclusions: Our results identified that in early stage HIV-1 infection, a subtype of T cells, CD4⁺CD8^low, are associated with subsequent disease progression.

Keywords: CD4+CD8low T cells; Primary HIV-1 infection; Rapid disease progression.