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Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells.

Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, Grusby MJ - J. Exp. Med. (2002)

Bottom Line: Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo.IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression.These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-gamma-producing Th1 cells which could serve to amplify a Th2 response.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

ABSTRACT
The cytokine potential of developing T helper (Th) cells is directly shaped both positively and negatively by the cytokines expressed by the effector Th cell subsets. Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo. Exposure of naive Th precursors to IL-21 inhibits interferon (IFN)-gamma production from developing Th1 cells. The repression of IFN-gamma production is specific in that the expression of other Th1 and Th2 cytokines is unaffected. IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression. These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-gamma-producing Th1 cells which could serve to amplify a Th2 response.

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IL-21 is a Th2 cytokine. (A) Thp cells were cultured under Th1 and Th2 skewing conditions for 6 d. The cells were left resting (−) or restimulated with PMA/Ionomycin (P+I) for 4 h. Similar results were observed for 6 and 24 h after stimulation (unpublished data). RNA was purified and assessed for cytokine expression by Northern blot analysis. The results shown are representative of three independent experiments. (B) Thp cells were cultured under neutral, Th1, and Th2 skewing conditions. RNA was purified 24 h after primary and secondary anti-CD3 stimulation. Cytokine expression was assessed in duplicate by RealTime PCR and shown relative to GAPDH. (C) Thp cells were cultured under Th1 and Th2 skewing conditions for 5 d. IL-4 or IFN-γ were added to indicated cultures 24 h before secondary stimulation with anti-CD3. RNA was purified 24 h after secondary stimulation and IL-21 expression was assessed in duplicate and shown relative to GAPDH by RealTime PCR. (D) Cohorts of eight BALB/c and C57BL/6 mice were infected with L. major in hind footpads. After 6 wk CD4+ T cells from draining lymph nodes were purified and stimulated with anti-CD3. RNA was purified 6 h after stimulation and cytokine expression was assessed relative to GAPDH by RealTime PCR.
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fig1: IL-21 is a Th2 cytokine. (A) Thp cells were cultured under Th1 and Th2 skewing conditions for 6 d. The cells were left resting (−) or restimulated with PMA/Ionomycin (P+I) for 4 h. Similar results were observed for 6 and 24 h after stimulation (unpublished data). RNA was purified and assessed for cytokine expression by Northern blot analysis. The results shown are representative of three independent experiments. (B) Thp cells were cultured under neutral, Th1, and Th2 skewing conditions. RNA was purified 24 h after primary and secondary anti-CD3 stimulation. Cytokine expression was assessed in duplicate by RealTime PCR and shown relative to GAPDH. (C) Thp cells were cultured under Th1 and Th2 skewing conditions for 5 d. IL-4 or IFN-γ were added to indicated cultures 24 h before secondary stimulation with anti-CD3. RNA was purified 24 h after secondary stimulation and IL-21 expression was assessed in duplicate and shown relative to GAPDH by RealTime PCR. (D) Cohorts of eight BALB/c and C57BL/6 mice were infected with L. major in hind footpads. After 6 wk CD4+ T cells from draining lymph nodes were purified and stimulated with anti-CD3. RNA was purified 6 h after stimulation and cytokine expression was assessed relative to GAPDH by RealTime PCR.

Mentions: Although IL-21 has been reported to have a wide range of effects on a number of cell types, the only reported source of IL-21 thus far is activated CD4+ T cells (7). To determine if IL-21 is expressed exclusively within Th cell subsets, Northern blot analysis was performed on mRNA from naive Thp cells differentiated into Th1 or Th2 cells for 1 wk and restimulated for 4 h to induce cytokine production. IL-21 mRNA was undectable in Th1 cell cultures, but induced in Th2 cells suggesting that IL-21 is a Th2 cytokine (Fig. 1 A).


Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon gamma-producing Th1 cells.

Wurster AL, Rodgers VL, Satoskar AR, Whitters MJ, Young DA, Collins M, Grusby MJ - J. Exp. Med. (2002)

IL-21 is a Th2 cytokine. (A) Thp cells were cultured under Th1 and Th2 skewing conditions for 6 d. The cells were left resting (−) or restimulated with PMA/Ionomycin (P+I) for 4 h. Similar results were observed for 6 and 24 h after stimulation (unpublished data). RNA was purified and assessed for cytokine expression by Northern blot analysis. The results shown are representative of three independent experiments. (B) Thp cells were cultured under neutral, Th1, and Th2 skewing conditions. RNA was purified 24 h after primary and secondary anti-CD3 stimulation. Cytokine expression was assessed in duplicate by RealTime PCR and shown relative to GAPDH. (C) Thp cells were cultured under Th1 and Th2 skewing conditions for 5 d. IL-4 or IFN-γ were added to indicated cultures 24 h before secondary stimulation with anti-CD3. RNA was purified 24 h after secondary stimulation and IL-21 expression was assessed in duplicate and shown relative to GAPDH by RealTime PCR. (D) Cohorts of eight BALB/c and C57BL/6 mice were infected with L. major in hind footpads. After 6 wk CD4+ T cells from draining lymph nodes were purified and stimulated with anti-CD3. RNA was purified 6 h after stimulation and cytokine expression was assessed relative to GAPDH by RealTime PCR.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2194031&req=5

fig1: IL-21 is a Th2 cytokine. (A) Thp cells were cultured under Th1 and Th2 skewing conditions for 6 d. The cells were left resting (−) or restimulated with PMA/Ionomycin (P+I) for 4 h. Similar results were observed for 6 and 24 h after stimulation (unpublished data). RNA was purified and assessed for cytokine expression by Northern blot analysis. The results shown are representative of three independent experiments. (B) Thp cells were cultured under neutral, Th1, and Th2 skewing conditions. RNA was purified 24 h after primary and secondary anti-CD3 stimulation. Cytokine expression was assessed in duplicate by RealTime PCR and shown relative to GAPDH. (C) Thp cells were cultured under Th1 and Th2 skewing conditions for 5 d. IL-4 or IFN-γ were added to indicated cultures 24 h before secondary stimulation with anti-CD3. RNA was purified 24 h after secondary stimulation and IL-21 expression was assessed in duplicate and shown relative to GAPDH by RealTime PCR. (D) Cohorts of eight BALB/c and C57BL/6 mice were infected with L. major in hind footpads. After 6 wk CD4+ T cells from draining lymph nodes were purified and stimulated with anti-CD3. RNA was purified 6 h after stimulation and cytokine expression was assessed relative to GAPDH by RealTime PCR.
Mentions: Although IL-21 has been reported to have a wide range of effects on a number of cell types, the only reported source of IL-21 thus far is activated CD4+ T cells (7). To determine if IL-21 is expressed exclusively within Th cell subsets, Northern blot analysis was performed on mRNA from naive Thp cells differentiated into Th1 or Th2 cells for 1 wk and restimulated for 4 h to induce cytokine production. IL-21 mRNA was undectable in Th1 cell cultures, but induced in Th2 cells suggesting that IL-21 is a Th2 cytokine (Fig. 1 A).

Bottom Line: Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo.IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression.These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-gamma-producing Th1 cells which could serve to amplify a Th2 response.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.

ABSTRACT
The cytokine potential of developing T helper (Th) cells is directly shaped both positively and negatively by the cytokines expressed by the effector Th cell subsets. Here we find that the recently identified cytokine, interleukin (IL)-21, is preferentially expressed by Th2 cells when compared with Th1 cells generated in vitro and in vivo. Exposure of naive Th precursors to IL-21 inhibits interferon (IFN)-gamma production from developing Th1 cells. The repression of IFN-gamma production is specific in that the expression of other Th1 and Th2 cytokines is unaffected. IL-21 decreases the IL-12 responsiveness of developing Th cells by specifically reducing both signal transducer and activator of transcription 4 protein and mRNA expression. These results suggest that Th2 cell-derived IL-21 regulates the development of IFN-gamma-producing Th1 cells which could serve to amplify a Th2 response.

Show MeSH
Related in: MedlinePlus