The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/1/129/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 1, January 5, 1998 129-134

Brief Definitive Reports

Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s

Raffaella Bonecchi*, Giancarlo Bianchi*, Paola Panina Bordignon{ddagger}, Daniele D'Ambrosio{ddagger}, Rosmarie Lang{ddagger}, Alessandro Borsatti*, Silvano Sozzani*, Paola Allavena*, Patrick A. Gray§, Alberto Mantovani*,||, and Francesco Sinigaglia{ddagger}

From the * Istituto di Ricerche Farmacologiche "Mario Negri", I-20157 Milan, Italy; {ddagger} Roche Milano Ricerche, I-20132 Milan, Italy; § ICOS Corporation, Bothell, Washington 98021; and || Universita' di Brescia, I-25123 Brescia, Italy

T helper cells type 1 (Th1s) that produce interferon-{gamma} predominantly mediate cellular immune responses and are involved in the development of chronic inflammatory conditions, whereas Th2s which produce large amounts of IL-4 and IL-5 upregulate IgE production and are prominent in the pathogenesis of allergic diseases. The precise factors determining whether Th1- or Th2-mediated immune responses preferentially occur at a peripheral site of antigen exposure are largely unknown. Chemokines, a superfamily of polypeptide mediators, are a key component of the leukocyte recruitment process. Here we report that among four CXC (CXCR1-4) and five CC (CCR1-5) chemokine receptors analyzed, CXCR3 and CCR5 are preferentially expressed in human Th1s. In contrast, Th2s preferentially express CCR4 and, to a lesser extent, CCR3. In agreement with the differential chemokine receptor expression, Th1s and Th2s selectively migrate in response to the corresponding chemokines. The differential expression of chemokine receptors may dictate, to a large extent, the migration and tissue homing of Th1s and Th2s. It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors.

Address correspondence to Francesco Sinigaglia, Roche Milano Ricerche, Via Olgettina 58, I-20132 Milano, Italy. Phone: +39-2-2884803; Fax: +39-2-2153203; E-mail: francesco.sinigaglia@ roche.com


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