Downregulation of CD73 on CD4+ T cells from patients with chronic Chikungunya infection.

[Display omitted] • Coinhibitory receptors PD-1 and CTLA-4 are up-regulated during Acute Chikungunya. • In acute infection, CD4+ T cells produce high levels of cytokines IL-10 and IFN-γ. • CD39 and CD73 expressed by CD4+ T cells are downregulated in individuals with the persistence of symptoms. • Chronic Chikungunya is marked by the reduced density of perforin and granzyme B. • High levels of IL-10, IFN-γ, and CD39 and CD73 coexpression and diminished perforin + CD4+ T cells were found in individuals with edema during chronic Chikungunya. • Acute patients without arthralgia presented more cytolytic granules production. Chikungunya is an important mosquito-borne disease caused by the arthritogenic chikungunya virus, characterized by sporadic outbreaks all around the world. Although CD4+ T cells seem to have an important role in the pathogenesis of chikungunya, the mechanisms involved in this process are not yet fully elucidated. The ectoenzymes CD39 and CD73, also expressed by CD4 T lymphocytes, are involved in the hydrolysis of pro-inflammatory extracellular ATP and generation of immunosuppressive adenosine and seem to be modulated in some arthritogenic pathologies. However, their involvement in Chikungunya disease is unclear. Thus, using flow cytometry, we investigated peripheral CD4+ T cells from patients with acute and chronic chikungunya to assess the expression of ectonucleotidases CD39 and CD73 and coinhibitory receptors and production of cytokine and cytolytic granules. Patients in the acute phase displayed increased levels of PD-1, CTLA-4, IL-10, and IFN-γ compared to healthy individuals and patients in the chronic phase. Moreover, during chronic Chikungunya, analyses of Mean Fluorescent Intensity (MFI) demonstrated a reduced density of LAP, Perforin and Granzyme B compared to the healthy control. Finally, reduced levels of the ectoenzymes CD39 and CD73 expression was found during the chronic phase suggesting a possible modulation of extracellular ATP and adenosine by CD4+ T cells that may be involved in the persistence of arthritogenic symptoms. [ABSTRACT FROM AUTHOR]