Defective eosinophil chemotaxis to eotaxin in a patient with chronic lower baseline CD4⁺ T-lymphocytes and elevated CD8⁺ T cells

Amr E El-Shazly¹, Monique Henket², Philippe P Lefebvre¹, Renaud Louis²

¹Department of Oto-Rhino-Laryngology and Head and Neck Surgery, GIGA-Research, Liege University Hospitals (Centre Hospitalier Universaitaire-C.H.U.). Liege-Belgium; ²Department of Pulmonology, GIGA-Research, Liege University Hospitals (Centre Hospitalier Universaitaire-C.H.U.). Liege-Belgium

Background: Idiopathic selective CD4⁺ lower baseline cell count and an increase in CD8⁺ cells is an unusual immune defect. Whether this is a true variant of idiopathic CD4⁺ T lymphocytopenia (ICL) or a sequelae to recurrent infections is not clear.

Objectives: The primary objective of this study was to investigate the expression and function of the cc-chemokine receptor CCR3 in eosinophils from a female patient with this disorder. A secondary objective was to study the in vitro ability of different cytokines to modulate the reversed CD4:CD8 ratio in this syndrome. Participants: A female patient suffering cellular immune defect with chronic lower baseline CD4⁺ counts with persistent increase in CD8⁺ cells, and positive skin test and radioallergosorbent test to pollens. Seven volunteers served as controls: five healthy subjects and two allergic volunteers (one asthmatic and one rhinitic).

Results: The patient’s eosinophils had defective chemotaxis, shape changes, and F-actin reorganization against eotaxin, when compared to the controls. CCR3 surface and total expression was highest in allergic subjects and least in the patient with cellular immune defect. Culture of eosinophils with interleukin-7 (IL-7), but not IL-2 for 24 hours resulted in increased expression of CCR3 in both the patient and controls as evidenced by fluorescence-activated cell scanning (FACS) analysis. Confocal microscopy demonstrated cytoskeletal changes and F-actin reorganization of the patient’s eosinophils only after treatment with IL-7. Culture of the patient’s lymphocytes with IL-2, IL-7, IL-10, IL-17, IL-15, or phytohemagglutinin increased the number of the patient’s CD4⁺-expressing lymphocytes as measured by FACS analysis. The potency of correcting the CD4:CD8 ratio from a baseline of 0.5 was highest with IL-10, followed by IL-15, while the rest of the cytokines had a similar ratio, being 0.8, 0.7, and 0.6, respectively.

Conclusions: Taken collectively, our preliminary results may indicate a novel role for IL-7 in enhancing the CCR3 expression and function in patients of this syndrome and highlights the novel role of IL-10 in inducing a significant increase in CD4⁺-expressing lymphocytes from the patient when compared to controls.

Keywords: eosinophil, defective chemotaxis, CCR3, eotaxin, CD4⁺:CD8⁺ Ratio, IL-7, IL-10