Role of γ/δ T cells in a patient with CD4+ CD3– lymphocytosis, hypereosinophilia, and high levels of IgE

Abstract

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 IU/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. (J Allergy Clin Immunol 1998;102:621-30.)