T-cell receptor-independent activation of clonal Th2 cells associated withchronic hypereosinophilia

We recently observed a clonal expansion of CD3(-)CD4(+) T cells secreting T h2-type cytokines in patients presenting chronic hypereosinophilia. As clon al T cells isolated from such patients did not spontaneously secrete cytoki nes in vitro, we reasoned that costimulatory signals delivered by antigen-p resenting cells might be required to induce their full activation. To addre ss this question, we investigated in two such patients the responses of CD3 (-)CD4+ T cells to dendritic cells (DC). DC elicited proliferation and prod uction of interleukin-5 (IL-5) and IL-13 by clonal cells from patient 1 and upregulated their expression of CD25 (IL-2R-alpha). These effects were abo lished when blocking monoclonal antibodies (MoAbs) against IL-2R-alpha and IL-2 were added to cocultures, indicating critical involvement of an autocr ine IL-2/IL-2R pathway. Cells from patient 2 were stimulated by DC to produ ce Th2 cytokines only when rIL-2 or rIL-15 was added to cocultures. In both patients, addition of inhibitory MoAbs against B7-1/B7-2 or CD2 to cocultu res resulted in dramatic reduction of cytokine production and inhibited CD2 5 upregulation. Thus, TCR/CD3-independent activation of clonal Th2 cells by DC is an IL-2-dependent process, which requires signaling through CD2 and CD28. (C) 1999 by The American Society of Hematology.