T-Cell Receptor-Independent Activation of Clonal Th2 Cells Associated With Chronic Hypereosinophilia

We recently observed a clonal expansion of CD3−CD4+ T cells secreting Th2-type cytokines in patients presenting chronic hypereosinophilia. As clonal T cells isolated from such patients did not spontaneously secrete cytokines in vitro, we reasoned that costimulatory signals delivered by antigen-prese...

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Bibliographic Details
Published in:Blood 1999-08, Vol.94 (3), p.994-1002
Main Authors: Roufosse, Florence, Schandené, Liliane, Sibille, Catherine, Kennes, Bernard, Efira, André, Cogan, Elie, Goldman, Michel
Format: Article
Language:English
Subjects:
Adult
AIDS/HIV
Biological and medical sciences
CD3 Complex
CD4 Antigens
Cell Differentiation - immunology
Clone Cells - immunology
Cytokines - immunology
Eosinophilia - immunology
Eosinophilia - pathology
Female
Hematologic and hematopoietic diseases
Humans
Lymphocyte Activation
Medical sciences
Other diseases. Hematologic involvement in other diseases
Receptors, Antigen, T-Cell - immunology
Th2 Cells - immunology
Th2 Cells - pathology
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Summary:We recently observed a clonal expansion of CD3−CD4+ T cells secreting Th2-type cytokines in patients presenting chronic hypereosinophilia. As clonal T cells isolated from such patients did not spontaneously secrete cytokines in vitro, we reasoned that costimulatory signals delivered by antigen-presenting cells might be required to induce their full activation. To address this question, we investigated in two such patients the responses of CD3−CD4+ T cells to dendritic cells (DC). DC elicited proliferation and production of interleukin-5 (IL-5) and IL-13 by clonal cells from patient 1 and upregulated their expression of CD25 (IL-2R-α). These effects were abolished when blocking monoclonal antibodies (MoAbs) against IL-2R-α and IL-2 were added to cocultures, indicating critical involvement of an autocrine IL-2/IL-2R pathway. Cells from patient 2 were stimulated by DC to produce 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 cocultures resulted in dramatic reduction of cytokine production and inhibited CD25 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V94.3.994.415k26_994_1002