Role of γ/δT cells in a patient with CD4⁺CD3^- lymphocytosis, hypereosinophilia, and high levels of IgE

Background: CD4⁺CD3^- T cells have previously been shown to play a pathogenic role in the hypereosinophilic syndrome by secreting IL-5 and IL-4. Objectives: The goal of this study was to study the role of CD4⁺CD3^- and other T-cell subsets in a patient with eosinophilia, dermatitis, and a high level of IgE (100,000 lU/mL) in the serum. Methods: We isolated PBMCs and performed flow cytometry, cell cultures, and in vitro assays of Ig, lymphokine production, and cell-mediated cytotoxicity. Results: Flow cytometric and immunohistochemical analysis of the PBMCs revealed a major population (consisting of approximately 85% of the CD4⁺ T cells) that lacked expression of CD3 and T-cell receptors on the cell surface (CD4⁺CD3^- T cells), but did express CD3 peptides in the cytoplasm. Activation of the PBMCs in vitro resulted in a 100-fold greater than normal release of IL-4, whereas IFN-γ production was less than normal, suggesting a predominantly type 2 helper functional phenotype of the CD4⁺CD3^- T cells. Importantly, both CD4^-CD8^low Vδ1⁺ T-cell receptor γδ⁺ and CD4⁺CD3^- T cells were cultured from the PBMCs. The former secreted IFN-γ exclusively, whereas the latter secreted both IL-4 and IFN-γ. Furthermore, only the T-cell receptor γδ⁺ lymphocytes were cytotoxic to autologous B-lymphoblastoid cells and specifically inhibited IgE production in cultures of autologous polyclonally stimulated PBMCs. Conclusions: The results suggest that CD8^low Vδ1⁺ T-cell receptor γδ⁺ clones functionally counteract IgE-inducing effects of type 2 CD4⁺CD3^- helper cells in this patient with hypereosinophilic syndrome.