The hypereosinophilic syndrome associated with CD4(+)CD3(-) helper type 2 (Th2) lymphocytes

We describe herein the clinical and laboratory manifestations of a unique g roup of patients (pts) presenting with hypereosinophilic syndrome (HES) who were treated in our medical centers for 4-13 years. Skin biopsies, flow cy tometry of peripheral blood mononuclear cells (PBMC), assays for cytokines and immunoglobulin (Ig) production in vitro, and Southern blots of T-cell r eceptor (TCR) genes were performed. All four pts had a persistent hypereosi nophilia (>1.9x10(9)/L and chronic skin rash. Three of four had elevated Ig E, thrombotic manifestations and lung involvement (asthma and/or infiltrate s), and one had deforming sero-negative arthritis of the hands. 66-95% of t heir peripheral T-cells expressed CD4 but not CD3 or TCR molecules on the c ell surface membrane. Activated CD4(+)CD3(-) cells secreted interleukin (IL )- 4 and/or 5, and were required for maximal IgE secretion by autologous B- cells. Two pts had evidence of rearrangement of TCR genes of the CD4(+)CD3( -) cells, one of whom died of anaplastic lymphoma. In conclusion, HES with CD4(+)CD3(-) lymphocytosis may be associated with high serum IgE, dermatolo gical, pulmonary, thrombotic and rheumatic manifestations which may be due to Th2 effects of CD4(+)CD3(-) cells migrating to end organs. Fatal systemi c lymphoid malignancy may also develop in some pts with monoclonal expansio n of the CD4(+)CD3(-) T-cells.