Defective Lymphoid Development in Mice Lacking Jak3

Nosaka, Tetsuya; Deursen, Jan M. A. van; Tripp, Ralph A.; Thierfelder, William E.; Witthuhn, Bruce A.; McMickle, Anthony; Doherty, Peter C.; Grosveld, Gerard

doi:10.1126/science.270.5237.800

Cited by 611 publications

(364 citation statements)

References 22 publications

Supporting

Mentioning

345

Contrasting

Unclassified

Order By: Relevance

“…However, it remains unproven which JAK is responsible for phosphorylation of IL2Rb vs Stat5 proteins in vivo. What is clear, however, is that both JAKs are required for normal IL-2-mediated Stat5 activation (Nosaka et al, 1995;Park et al, 1995;Rodig et al, 1998;Thomis et al, 1995).…”

Section: How Are Stat5 Proteins Activated By Il-2 Family Cytokines?mentioning

confidence: 99%

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

2000

View full text Add to dashboard Cite

Section: How Are Stat5 Proteins Activated By Il-2 Family Cytokines?mentioning

confidence: 99%

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

2000

View full text Add to dashboard Cite

“…In contrast, differentiation of T lineage cells in the thymus appears to progress relatively normally in the absence of Jak3 or ␥c, based on the analysis of CD4/CD8 subsets; however, the thymuses of these KO mice are severely hypoplastic [18][19][20][21][22][23]. Compared to wild-type mice, the cellularity of a Jak3-or ␥c-deficient thymus is reduced by 10-to 100-fold.…”

Section: Introductionmentioning

confidence: 99%

T cell development and activation in Jak3-deficient mice

Baird

Thomis

Berg

1998

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Jak3, a member of the Janus family of tyrosine kinases, participates in signaling through cytokine receptors that contain the common ␥-chain, including the receptors for interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15. Jak3-and ␥c-deficient mice have pleiotropic defects that can be attributed to their inability to respond to multiple specific cytokines. A great deal of recent work has focused on the T cell defects in these mutant mice. Specifically, Jak3-and ␥c-deficient mice have small thymuses revealing a defect in T cell development, and in addition, have functionally unresponsive peripheral T cells with an activated/memory cell phenotype. The thymic defect in these mutant mice strongly resembles that seen in IL-7 and IL-7 receptor knockout mice, suggesting that the lack of IL-7 receptor signaling accounts for this defect in Jak3 -/-and ␥c ؊ mice. To characterize this defect further, we have examined the earliest stages of T cell development in adult and fetal Jak3 -/-thymuses. These studies identify two discrete developmental defects at the CD4 ؊ CD8 ؊ stage of T cell maturation. Analyses of peripheral T cells in Jak3 -/-and ␥c ؊ mice have also revealed a number of abnormalities. All of the T cells in these mutant mice have an activated phenotype and a large fraction of them are proliferating in vivo. In addition, Jak3 -/-and ␥c ؊ T cells are more prone to undergo apoptosis than wild-type T cells. Together, these features account for the decreased IL-2 secretion by in vitro-stimulated Jak3 -/-T cells. Overall, many of the lymphoid defects of Jak3-and ␥c-deficient mice can be accounted for by the lack of IL-7R and IL-2R signaling; however, other cytokine systems must also be involved in maintaining peripheral T cell homeostasis.

show abstract

“…Studies of gene-targeted mice have provided much of the evidence implicating specific cytokines in ␣␤ T cell, ␥␦ T cell, or NK cell development. For instance, mice lacking IL-7 or components of the IL-7R signaling pathway (i.e., IL-7R␣, common ␥-chain (␥c), 3 or Jak3) fail to develop ␥␦ T cells (1)(2)(3)(4)(5)(6)(7). IL-15R signaling has been shown to be critical for NK cell development, as IL-15R␣-, ␥c-, and Jak3-deficient mice all lack NK cells (4 -10).…”

Section: A Profound Deficiency In Thymic Progenitormentioning

confidence: 99%

A Profound Deficiency in Thymic Progenitor Cells in Mice Lacking Jak3

Baird

Lucas

Berg

2000

The Journal of Immunology

View full text Add to dashboard Cite

Humans and mice with genetic deficiencies that lead to loss of signaling through common γ-chain (γc)-containing cytokine receptors have severe defects in B and T lymphocytes. In humans, these deficiencies lead to a complete absence of T cells, whereas in mice, small thymuses give rise to normal numbers of peripheral T cells. We have examined the first wave of developing T cells in Jak3−/−, IL-7−/−, and IL-7Rα−/− fetal mice, and have found a near absence of thymic progenitor cells. This deficiency is highlighted by the complete inability of Jak3−/− progenitor cells to reconstitute T cell development in the presence of competing wild-type cells. These data clearly demonstrate a strong common basis for the T cell deficiencies in mice and humans lacking γc/Jak3 signaling pathways.

show abstract

Defective Lymphoid Development in Mice Lacking Jak3

Cited by 611 publications

References 22 publications

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

The role of Stat5a and Stat5b in signaling by IL-2 family cytokines

T cell development and activation in Jak3-deficient mice

A Profound Deficiency in Thymic Progenitor Cells in Mice Lacking Jak3

Contact Info

Product

Resources

About