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-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-alpha). These effects were abolished when blocking monoclonal antibodies (MoAbs) against IL-2R-alpha 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.
Roufosse
F
F
Departments of Immunology and Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Schandené
L
L
Sibille
C
C
Kennes
B
B
Efira
A
A
Cogan
E
E
Goldman
M
M
D000328:Adult; D017252:CD3 Complex; D015704:CD4 Antigens; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D017252:CD3 Complex; D015704:CD4 Antigens; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell