# CD4 and CD8 T-cell response is dominated by IL-10–secreting cells in children with uncomplicated Plasmodium falciparum malaria

## TL;DR

This study finds that acute malaria in children causes T-cells to secrete more IL-10, a suppressive cytokine, which may weaken immune control of viruses like EBV.

## Contribution

The study reveals that malaria-induced immune changes are systemic, not EBV-specific, and involve increased IL-10 secretion by T-cells.

## Key findings

- T-cell activation levels were similar in malaria-affected children and controls.
- Malaria caused a shift toward IL-10 secretion in both CD4 and CD8 T-cells.
- Immune suppression from malaria was not limited to EBV-specific responses.

## Abstract

Plasmodium falciparum malaria and Epstein-Barr virus (EBV) coinfections have been associated with an increased risk of developing the EBV-associated cancer endemic Burkitt lymphoma (eBL). In children living in malaria-endemic areas, repeated episodes of malaria may alter the immune system’s ability to suppress EBV, creating a permissive environment for eBL pathogenesis. However, the malaria-driven mechanisms involved remain undefined, including whether malaria-induced immune alterations are EBV-specific or systemic. To identify whether acute clinical P. falciparum malaria affects EBV T-cell immunity, we characterized T-cell activation status and cytokine secretion profiles using flow cytometry. We compared profiles in 10 Kenyan children with acute clinical P. falciparum malaria at baseline and matched 4-week recovery, and 10 healthy community controls following antigenic stimulation with EBV- and cytomegalovirus-specific peptides. The percentage frequency of activation-induced marker cells was comparable within the study cohort across the different stimulations. Furthermore, we observed a shift in cytokine secretion in children with acute malaria during active disease and at 4 weeks postrecovery, favoring IL-10 for both T-cell subsets. Our findings suggest that clinical malaria did not result in the impairment of T-cell activation, but rather induced shifts in cytokine secretion in favor of IL-10. We further demonstrate that malaria-induced T-cell immune alterations are not EBV-specific but rather affect overall immune suppression.