Increased Activation and Oligoclonality of Peripheral CD8 + T Cells in the Chronic Human Helminth Infection Alveolar Echinococcosis

Abstract

ABSTRACT Alveolar echinococcosis (AE) in humans is a chronic disease characterized by slowly expanding liver lesions. Cellular immunity restricts the spreading of the extracellular pathogen, but functional contributions of CD4 + and CD8 + T cells are not defined. Here we studied ex vivo the phenotype and function of circulating T-cell subsets in AE patients by means of flow cytometry, T-cell receptor spectratyping, and lymphocyte proliferation. AE patients with parasitic lesions displayed a significant increase of activation of predominantly CD8 + T cells compared to healthy controls and AE patients without lesions. In vitro, proliferative T-cell responses to polyclonal stimulation with recall antigens and Echinococcus multilocularis vesicular fluid antigen were sustained during chronic persisting infection in all AE patients. Only in AE patients with parasitic lesions did T-cell receptor spectratyping reveal increased oligoclonality of CD8 + but not CD4 + T cells, suggesting a persistent antigenic drive for CD8 + T cells with subsequent proliferation of selected clonotypes. Thus, our data provide strong evidence for an active role of CD8 + T cells in AE.