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Selective expression of an interleukin-12 receptor component by human T helper 1 cells.

Rogge L, Barberis-Maino L, Biffi M, Passini N, Presky DH, Gubler U, Sinigaglia F - J. Exp. Med. (1997)

Bottom Line: Here we show that the IL-12 receptor (IL-12R) beta 2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway.IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering.The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.

View Article: PubMed Central - PubMed

Affiliation: Roche Milano Ricerche, Italy.

ABSTRACT
Interleukin-12 (IL-12), a heterodimeric cytokine produced by activated monocytes and dendritic cells, plays a crucial role in regulating interferon (IFN)-gamma production and in the generation of IFN-gamma-producing T helper 1 (Th1) cells. Here we show that the IL-12 receptor (IL-12R) beta 2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway. IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering. The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.

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Scatchard analysis of  [125I]IL-12 binding to human  Th1 and Th2 cell lines. Th1 and  Th2 lines were generated as described above. Scatchard analysis  was performed using [125I]labeled  human IL-12 binding on human  Th1 and Th2 cell lines on day 9  after priming as described in Materials and Methods. Comparable  [125I]IL- 12 binding data were  obtained in three independently  derived Th1 and Th2 cell lines.
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Figure 5: Scatchard analysis of [125I]IL-12 binding to human Th1 and Th2 cell lines. Th1 and Th2 lines were generated as described above. Scatchard analysis was performed using [125I]labeled human IL-12 binding on human Th1 and Th2 cell lines on day 9 after priming as described in Materials and Methods. Comparable [125I]IL- 12 binding data were obtained in three independently derived Th1 and Th2 cell lines.

Mentions: We next analyzed IL-12R expression by radioligand binding assays. Scatchard analysis of specific [125I]IL-12 binding to human cord blood derived Th1 and Th2 cell lines is shown in Fig. 5. In Th1 cell lines, both high (KD of 27 pM, 140 sites/cell) and low affinity (KD of 5 nM, 450 sites/cell) [125I]IL-12 binding sites were measured. In contrast, Th2 cells lines exhibited only low affinity [125I]IL-12 binding sites (KD of 2 nM 220 sites/cell). The absence of measurable high affinity [125I]IL-12 binding to the human Th2 cell lines is in agreement with the observed lack of IL-12R β2 expression in these cells. On the contrary, similar levels of high and low affinity IL-12 binding were measured in mouse Th1 and Th2 cell lines (30 and data not shown). This difference in IL-12 binding behavior in the mouse and human systems may reflect the dominant role mouse IL-12R β1 plays in binding IL-12 (34), whereas in humans, both IL-12R β1 and β2 appear to contribute equally to IL-12 binding (25). These results demonstrate that the IL-12R β2 subunit is selectively expressed in Th1 cells where it is induced upon T cell activation. Moreover, our data suggest that the lack of IL-12R β2 chain expression could be the reason underlying the inability of IL-12 to activate the Jak2-Stat4 pathway in Th2 cells.


Selective expression of an interleukin-12 receptor component by human T helper 1 cells.

Rogge L, Barberis-Maino L, Biffi M, Passini N, Presky DH, Gubler U, Sinigaglia F - J. Exp. Med. (1997)

Scatchard analysis of  [125I]IL-12 binding to human  Th1 and Th2 cell lines. Th1 and  Th2 lines were generated as described above. Scatchard analysis  was performed using [125I]labeled  human IL-12 binding on human  Th1 and Th2 cell lines on day 9  after priming as described in Materials and Methods. Comparable  [125I]IL- 12 binding data were  obtained in three independently  derived Th1 and Th2 cell lines.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196163&req=5

Figure 5: Scatchard analysis of [125I]IL-12 binding to human Th1 and Th2 cell lines. Th1 and Th2 lines were generated as described above. Scatchard analysis was performed using [125I]labeled human IL-12 binding on human Th1 and Th2 cell lines on day 9 after priming as described in Materials and Methods. Comparable [125I]IL- 12 binding data were obtained in three independently derived Th1 and Th2 cell lines.
Mentions: We next analyzed IL-12R expression by radioligand binding assays. Scatchard analysis of specific [125I]IL-12 binding to human cord blood derived Th1 and Th2 cell lines is shown in Fig. 5. In Th1 cell lines, both high (KD of 27 pM, 140 sites/cell) and low affinity (KD of 5 nM, 450 sites/cell) [125I]IL-12 binding sites were measured. In contrast, Th2 cells lines exhibited only low affinity [125I]IL-12 binding sites (KD of 2 nM 220 sites/cell). The absence of measurable high affinity [125I]IL-12 binding to the human Th2 cell lines is in agreement with the observed lack of IL-12R β2 expression in these cells. On the contrary, similar levels of high and low affinity IL-12 binding were measured in mouse Th1 and Th2 cell lines (30 and data not shown). This difference in IL-12 binding behavior in the mouse and human systems may reflect the dominant role mouse IL-12R β1 plays in binding IL-12 (34), whereas in humans, both IL-12R β1 and β2 appear to contribute equally to IL-12 binding (25). These results demonstrate that the IL-12R β2 subunit is selectively expressed in Th1 cells where it is induced upon T cell activation. Moreover, our data suggest that the lack of IL-12R β2 chain expression could be the reason underlying the inability of IL-12 to activate the Jak2-Stat4 pathway in Th2 cells.

Bottom Line: Here we show that the IL-12 receptor (IL-12R) beta 2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway.IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering.The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.

View Article: PubMed Central - PubMed

Affiliation: Roche Milano Ricerche, Italy.

ABSTRACT
Interleukin-12 (IL-12), a heterodimeric cytokine produced by activated monocytes and dendritic cells, plays a crucial role in regulating interferon (IFN)-gamma production and in the generation of IFN-gamma-producing T helper 1 (Th1) cells. Here we show that the IL-12 receptor (IL-12R) beta 2 subunit, a recently cloned binding and signal transducing component of the IL-12R, is expressed on human Th1 but not Th2 clones and is induced during differentiation of human naive cells along the Th1 but not the Th2 pathway. IL-12 and type I but not type II interferons induce expression of the IL-12R beta 2 chain during in vitro T cell differentiation after antigen receptor triggering. The selective expression and regulation of the IL-12R beta 2 subunit may help to understand the basis of Th1/Th2 differentiation and may provide therapeutic options for altering the Th1/Th2 balance in several immuno-pathological conditions such as autoimmune diseases and allergies.

Show MeSH
Related in: MedlinePlus