Expansion of multiple CD4+ T cell lineages in lymphocytic variant hypereosinophilic syndrome.

Abstract

BACKGROUND Lymphocytic variant hypereosinophilic syndrome (LHES) is a rare disorder characterized by hypereosinophilia, the presence of phenotypically aberrant populations of Th2 lymphocytes and varied clinical manifestations. Although disease pathogenesis has historically been attributed to IL-5 driven hypereosinophilia, response to eosinophil-lowering biologics is not universal, suggesting a more direct role for the aberrant lymphocyte population in disease pathogenesis. OBJECTIVE To further delineate the surface phenotypes and cytokine profiles of the aberrant lymphocyte populations in patients with LHES METHODS: Multiparameter flow cytometry was used to analyze lymphocytes in whole blood and stored peripheral blood mononuclear cells from a cohort of 42 untreated and treated patients with LHES. RESULTS Surface receptor profiling of the aberrant population in 22 untreated patients with LHES, including 8 patients with episodic angioedema with eosinophilia (EAE), confirmed prior data demonstrating that the aberrant CD4+ T cell populations in LHES have a Th2 memory phenotype. CCR8 was identified as a dominant surface marker, unaffected by sample processing or patient treatment status. Serum levels of CCL1, the ligand for CCR8 were increased in LHES patients compared to patients with other HES subtypes. Expanded populations of Foxp3+Helios+CCR8+ regulatory T cells were identified in many patients with CD3loCD4+ LHES and correlated with the size of the CD3loCD4+ population. CONCLUSION These data provide further evidence for direct involvement of the aberrant T cell populations in disease pathogenesis in LHES and a rationale for further exploration of T cell-directed therapies.