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Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.

Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F - J. Exp. Med. (1998)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Ricerche Farmacologiche "Mario Negri", I-20157 Milan, Italy.

ABSTRACT
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.

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Related in: MedlinePlus

Migratory response of Th1s and Th2s to chemokines. Migration was assessed in nitrocellulose filters as described (26). Spontaneous  migration was subtracted. Results are the mean of three (MDC, MCP-1),  two (eotaxin, IP-10), or one (MIP-1α, MIP-1β) experiment. The IP-10  dose response was obtained with one Th1 (ET3.20) and one Th2 (E4.1)  clone; bulk Th1 and Th2 lines were only tested at one concentration,  with similar results.
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Figure 4: Migratory response of Th1s and Th2s to chemokines. Migration was assessed in nitrocellulose filters as described (26). Spontaneous migration was subtracted. Results are the mean of three (MDC, MCP-1), two (eotaxin, IP-10), or one (MIP-1α, MIP-1β) experiment. The IP-10 dose response was obtained with one Th1 (ET3.20) and one Th2 (E4.1) clone; bulk Th1 and Th2 lines were only tested at one concentration, with similar results.

Mentions: Having established that chemokine receptors are differentially expressed in Th1s versus Th2s, we wanted to evaluate the functional significance of this observation. As shown in Fig. 4, consistent with receptor expression, MIP-1α (CCR1 agonist) and MCP-1 (a selective CCR2 agonist) showed comparable chemotactic activity for Th1s and Th2s. In contrast, MDC (19; a selective CCR4 agonist) was at least 10 times more active on Th2s versus Th1s, whereas MIP-1β (CCR5) and IP-10 (CXCR3) were more active on Th1s. Eotaxin (a selective CCR3 agonist) was inactive or weakly active only on Th2s. Thus, as expected on the basis of receptor expression, certain chemokines show differential action on Th1s and Th2s.


Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.

Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F - J. Exp. Med. (1998)

Migratory response of Th1s and Th2s to chemokines. Migration was assessed in nitrocellulose filters as described (26). Spontaneous  migration was subtracted. Results are the mean of three (MDC, MCP-1),  two (eotaxin, IP-10), or one (MIP-1α, MIP-1β) experiment. The IP-10  dose response was obtained with one Th1 (ET3.20) and one Th2 (E4.1)  clone; bulk Th1 and Th2 lines were only tested at one concentration,  with similar results.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199181&req=5

Figure 4: Migratory response of Th1s and Th2s to chemokines. Migration was assessed in nitrocellulose filters as described (26). Spontaneous migration was subtracted. Results are the mean of three (MDC, MCP-1), two (eotaxin, IP-10), or one (MIP-1α, MIP-1β) experiment. The IP-10 dose response was obtained with one Th1 (ET3.20) and one Th2 (E4.1) clone; bulk Th1 and Th2 lines were only tested at one concentration, with similar results.
Mentions: Having established that chemokine receptors are differentially expressed in Th1s versus Th2s, we wanted to evaluate the functional significance of this observation. As shown in Fig. 4, consistent with receptor expression, MIP-1α (CCR1 agonist) and MCP-1 (a selective CCR2 agonist) showed comparable chemotactic activity for Th1s and Th2s. In contrast, MDC (19; a selective CCR4 agonist) was at least 10 times more active on Th2s versus Th1s, whereas MIP-1β (CCR5) and IP-10 (CXCR3) were more active on Th1s. Eotaxin (a selective CCR3 agonist) was inactive or weakly active only on Th2s. Thus, as expected on the basis of receptor expression, certain chemokines show differential action on Th1s and Th2s.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Istituto di Ricerche Farmacologiche "Mario Negri", I-20157 Milan, Italy.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus