Phenotypic profiling of CD8+ T cells during plasmodium vivax blood-stage infection

Abstract

Background: For a long time, the role of CD8+ T cells in blood-stage malaria was not considered important because erythrocytes do not express major histocompatibility complex (MHC) class I proteins. While recent evidences suggest that CD8+ T cells may play an important role during the erythrocytic phase of infection by eliminating parasites, CD8+ T cells might also contribute to modulate the host response through production of regulatory cytokines. Thus, the role of CD8+ T cells during blood-stage malaria is unclear. Here, we report the phenotypic profiling of CD8+ T cells subsets from patients with uncomplicated symptomatic P. vivax malaria. Methods: Blood samples were collected from 20 Plasmodium vivax-infected individuals and 12 healthy individuals. Immunophenotyping was conducted by flow cytometry. Plasma levels of IFN-γ, TNF-α and IL-10 were determined by ELISA/CBA. Unpaired t-test or Mann-Whitney test was used depending on the data distribution. Results: P. vivax-infected subjects had lower percentages and absolute numbers of CD8+CD45RA+ and CD8+CD45RO+ T cells when compared to uninfected individuals (p ≤ 0.0002). A significantly lower absolute number of circulating CD8+CD45+CCR7+ cells (p = 0.002) was observed in P. vivax-infected individuals indicating that infection reduces the number of central memory T cells. Cytokine expression was significantly reduced in the naïve T cells from infected individuals compared with negative controls, as shown by lower numbers of IFN-γ+ (p = 0.001), TNF-α+ (p < 0.0001) and IL-10+ (p < 0.0001) CD8+ T cells. Despite the reduction in the number of CD8+ memory T cells producing IFN-γ (p < 0.0001), P. vivax-infected individuals demonstrated a significant increase in memory CD8+TNF-α+ (p = 0.016) and CD8+IL-10+ (p = 0.004) cells. Positive correlations were observed between absolute numbers of CD8+IL-10+ and numbers of CD8+IFN-γ+ (p < 0.001) and CD8+TNF-α+ T cells (p= 0.0001). Finally, an increase in the plasma levels of TNF-a (p = 0.017) and IL-10 (p = 0.006) and a decrease in the IFN-γ plasma level (p ≤0.0001) were observed in the P. vivax-infected individuals. Conclusions: P. vivax infection reduces the numbers of different subsets of CD8+ T cells, particularly the memory cells, during blood-stage of infection and enhances the number of CD8+ memory T cells expressing IL-10, which positively correlates with the number of cells expressing TNF-α and IFN-γ.