![]() While γ c-dependent signals play multiple roles in lymphocyte development, Janus kinase 3 (Jak3) is the only molecule which is known to transduce γ c-dependent signals (reviewed in 21,22). Fifth, IL-7 may function as a co-factor for TCR rearrangement ( 18, 19), although its role in this process is controversial (reviewed in 20). Fourth, γ c-dependent signals may play a role in thymic selection since the requirement of γ c-dependent signals for T cell development differs depending on the affinity of the TCR for MHC ( 13). However, γ c appears to play additional important role(s) in thymocyte development beyond the induction of Bcl-2 because thymic cellularity in Bcl-2 transgenic γ c-deficient mice is increased, but still is only 12–20% of the normal level ( 13, 17). Third, γ c-dependent signals are also required for the normally occurring up-regulation of Bcl-2 expression from CD4 +CD8 + double- positive (DP) to CD4 single-positive (SP) thymocytes ( 13). Second, IL-7 signals are vital for providing anti-apoptotic signals for CD4 –CD8 – double-negative (DN) thymocytes, most likely at least in part by inducing Bcl-2 expression ( 14– 17). First, γ c-dependent signals are required for normal cell division of immature thymocytes ( 13). Analyses of mice lacking γ c, IL-7 or IL-7Rα revealed that γ c-dependent signals are involved in a number of important events in T cell development ( 5, 6, 10– 17). ![]() This phenotype is consistent with the importance of IL-7 signaling for thymic T cell development ( 5– 7) and with the importance of IL-15 for NK cell development ( 8, 9). The γ c gene is located on the X chromosome and when mutated results in X-linked severe combined immunodeficiency (XSCID) ( 4), a disease in which both T cell and NK cell development is profoundly diminished. The common cytokine receptor γ chain (γ c) is a shared component of the receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 ( 1– 3). These results indicate that Jak3 is absolutely essential for γ c-dependent T cell and B cell development, and for γ c-dependent prevention of thymocyte apoptosis.ĪPC allophycocyanin, γ c common cytokine receptor γ chain, DO10 DO11.10, DN double negative, DP double positive, Jak3 Janus kinase 3, PE phycoerythrin, PMA phorbol myristate acetate, SCID severe combined immunodeficiency, SP single positive, XSCID X-linked severe combined immunodeficiency Introduction Interestingly, although Bcl-2 induction was previously suggested to be Jak3-independent, IL-7 cannot induce Bcl-2 expression in CD4 single-positive (SP) thymocytes in either γ c – or Jak3 – mice nor can IL-7 rescue CD4 SP thymocytes from dexamethasone-induced cell death in γ c – or Jak3 – mice. With the exception that T and B cells in Jak3 – mice express high levels of γ c, the defects in thymocyte and peripheral T cell and B cell development are indistinguishable among γ c –, Jak3 – and γ c –Jak3 – mice. To clarify whether γ c-dependent cytokines can partially transduce their signals without Jak3, we compared lymphocyte development in γ c –, Jak3 –, and γ c and Jak3 double-deficient (γ c –Jak3 –) mice in the same genetic background. Nevertheless, certain differences have been suggested related to the range of actions of γ c and Jak3. The Janus family tyrosine kinase 3 (Jak3) is known to be associated with γ c, and the reported phenotypes of γ c-deficient (γ c –) and Jak3-deficient (Jak3 –) mice are similar, indicating that Jak3 is an essential transducer of γ c-dependent signals. The common cytokine receptor γ chain (γ c) is an essential receptor component for IL-2, IL-4, IL-7, IL-9 and IL-15, and thereby γ c-deficient mice exhibit impaired T cell and B cell development.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |