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Crucial role of Jak3 in negative selection of self-reactive T cells.

Saijo K, Park SY, Ishida Y, Arase H, Saito T - J. Exp. Med. (1997)

Bottom Line: In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age.All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca2+ response upon T cell receptor (TCR) stimulation.These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Biomedical Science, Chiba University School of Medicine, Inohana, Chuo-ku, Japan.

ABSTRACT
Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL-2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in mice and humans. In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age. However, we found that self-reactive T cells were not deleted in the thymus and the peripheral tissues in Jak3-deficient mice. All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca2+ response upon T cell receptor (TCR) stimulation. From the analysis of TCR-transgenic Jak3-deficient mice, only self-reactive T cells appeared to be in the activated state and anergic. These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells.

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Expression of activation markers on splenic T cells  from Jak3-deficient mice (A) and  DO-Tg·Jak3−/− mice (B). (A)  Staining profiles of CD69,  CD44, and Mel-14 on splenic T  cells from Jak3-deficient mice  (−/−) and wild-type littermates  (+/+). Cells were stained for either CD69, CD44, or Mel-14 in  addition to CD4 and CD8, and  the profiles were shown for  CD4+ T cells. The profiles for  CD8+ T cells were almost the  same as for CD4+ T cells. Thick  and thin lines indicated staining  with each Ab and control staining, respectively. (B) Expression  of CD44 (left) and Mel-14 (right)  on CD4+ splenic T cells from  DO-Tg (+/+) and DOTg·Jak3−/− (−/−) mice. (Top  left) Staining profiles with the  clonotypic mAb KJ1-26; cells  were divided into two groups,  KJ1-26 high and low. (Bottom  left) Thin and thick lines indicate  CD44 staining for KJ1-26 high  and low cells, respectively. (Top  right) Staining profiles with antiVβ8 mAb; cells were divided  into two groups, Vβ8 high and  low. (Bottom right) Thin and  thick lines indicate Mel-14 staining for Vβ8 high and low cells,  respectively.
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Figure 2: Expression of activation markers on splenic T cells from Jak3-deficient mice (A) and DO-Tg·Jak3−/− mice (B). (A) Staining profiles of CD69, CD44, and Mel-14 on splenic T cells from Jak3-deficient mice (−/−) and wild-type littermates (+/+). Cells were stained for either CD69, CD44, or Mel-14 in addition to CD4 and CD8, and the profiles were shown for CD4+ T cells. The profiles for CD8+ T cells were almost the same as for CD4+ T cells. Thick and thin lines indicated staining with each Ab and control staining, respectively. (B) Expression of CD44 (left) and Mel-14 (right) on CD4+ splenic T cells from DO-Tg (+/+) and DOTg·Jak3−/− (−/−) mice. (Top left) Staining profiles with the clonotypic mAb KJ1-26; cells were divided into two groups, KJ1-26 high and low. (Bottom left) Thin and thick lines indicate CD44 staining for KJ1-26 high and low cells, respectively. (Top right) Staining profiles with antiVβ8 mAb; cells were divided into two groups, Vβ8 high and low. (Bottom right) Thin and thick lines indicate Mel-14 staining for Vβ8 high and low cells, respectively.

Mentions: In addition to the existence of autoreactive T cells in thymus, spleen, and lymph node, all peripheral T cells from Jak3−/− mice were activated as determined by surface expression of several markers. These T cells expressed high levels of CD44 and CD69 (18–20) and a low level of Mel14, representing the phenotype of activated T cells (Fig. 2 A).


Crucial role of Jak3 in negative selection of self-reactive T cells.

Saijo K, Park SY, Ishida Y, Arase H, Saito T - J. Exp. Med. (1997)

Expression of activation markers on splenic T cells  from Jak3-deficient mice (A) and  DO-Tg·Jak3−/− mice (B). (A)  Staining profiles of CD69,  CD44, and Mel-14 on splenic T  cells from Jak3-deficient mice  (−/−) and wild-type littermates  (+/+). Cells were stained for either CD69, CD44, or Mel-14 in  addition to CD4 and CD8, and  the profiles were shown for  CD4+ T cells. The profiles for  CD8+ T cells were almost the  same as for CD4+ T cells. Thick  and thin lines indicated staining  with each Ab and control staining, respectively. (B) Expression  of CD44 (left) and Mel-14 (right)  on CD4+ splenic T cells from  DO-Tg (+/+) and DOTg·Jak3−/− (−/−) mice. (Top  left) Staining profiles with the  clonotypic mAb KJ1-26; cells  were divided into two groups,  KJ1-26 high and low. (Bottom  left) Thin and thick lines indicate  CD44 staining for KJ1-26 high  and low cells, respectively. (Top  right) Staining profiles with antiVβ8 mAb; cells were divided  into two groups, Vβ8 high and  low. (Bottom right) Thin and  thick lines indicate Mel-14 staining for Vβ8 high and low cells,  respectively.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196119&req=5

Figure 2: Expression of activation markers on splenic T cells from Jak3-deficient mice (A) and DO-Tg·Jak3−/− mice (B). (A) Staining profiles of CD69, CD44, and Mel-14 on splenic T cells from Jak3-deficient mice (−/−) and wild-type littermates (+/+). Cells were stained for either CD69, CD44, or Mel-14 in addition to CD4 and CD8, and the profiles were shown for CD4+ T cells. The profiles for CD8+ T cells were almost the same as for CD4+ T cells. Thick and thin lines indicated staining with each Ab and control staining, respectively. (B) Expression of CD44 (left) and Mel-14 (right) on CD4+ splenic T cells from DO-Tg (+/+) and DOTg·Jak3−/− (−/−) mice. (Top left) Staining profiles with the clonotypic mAb KJ1-26; cells were divided into two groups, KJ1-26 high and low. (Bottom left) Thin and thick lines indicate CD44 staining for KJ1-26 high and low cells, respectively. (Top right) Staining profiles with antiVβ8 mAb; cells were divided into two groups, Vβ8 high and low. (Bottom right) Thin and thick lines indicate Mel-14 staining for Vβ8 high and low cells, respectively.
Mentions: In addition to the existence of autoreactive T cells in thymus, spleen, and lymph node, all peripheral T cells from Jak3−/− mice were activated as determined by surface expression of several markers. These T cells expressed high levels of CD44 and CD69 (18–20) and a low level of Mel14, representing the phenotype of activated T cells (Fig. 2 A).

Bottom Line: In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age.All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca2+ response upon T cell receptor (TCR) stimulation.These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells.

View Article: PubMed Central - PubMed

Affiliation: Center for Biomedical Science, Chiba University School of Medicine, Inohana, Chuo-ku, Japan.

ABSTRACT
Jak3 mediates growth signals through cytokine receptors such as interleukin-2 (IL-2), IL-4, and IL-7, and its deficiency results in autosomal recessive SCID in mice and humans. In spite of the severely reduced number of lymphocytes in Jak3-deficient mice, the differentiation profile of thymocytes was normal and mature T cells accumulated in the periphery with age. However, we found that self-reactive T cells were not deleted in the thymus and the peripheral tissues in Jak3-deficient mice. All peripheral T cells were in the activation state and thus were unable to be activated further, as demonstrated by the failure of eliciting Ca2+ response upon T cell receptor (TCR) stimulation. From the analysis of TCR-transgenic Jak3-deficient mice, only self-reactive T cells appeared to be in the activated state and anergic. These findings demonstrate a crucial function of Jak3 in the negative selection of autoreactive T cells and the maintenance of functional peripheral T cells.

Show MeSH
Related in: MedlinePlus