Role of the intracellular domain of IL-7 receptor in T cell development.
Signals from the IL-7R are uniquely required for T cell development and maintenance, despite the resemblance of IL-7R to other cytokine receptors and the apparent sharing of common signaling pathways. This unique requirement could either reflect unique expression of IL-7R or IL-7, or it could indicate that the IL-7R delivers unique signals. To determine whether the IL-7R provided unique signals, we exchanged its intracellular domain with that of other cytokine receptors: IL-4R, IL-9R, and prolactin receptor (PRLR). Chimeric receptors were used to reconstitute development of IL-7R(-/-) hemopoietic progenitors by transducing the receptors in retroviral vectors. Whereas IL-7R(-/-) thymocytes are arrested at the double-negative stage, IL-4R, IL-9R, or PRLR all imparted some progression to the double-positive stage. IL-4R and PRLR gave only small numbers of thymocytes, whereas IL-9R gave robust alphabeta T cell development and reconstitution of peripheral CD4 and CD8 cells, indicating that it can duplicate many of the functions of IL-7R. However, IL-9R failed to reconstitute rearrangement of the TCRgamma locus or development of gammadelta T cells. Thus, the IL-7R signals required in the alphabeta T cell lineage (such as survival and proliferation) are not unique to this receptor, whereas rearrangement of the TCRgamma locus may require a signal that is not shared by other receptors.
Jiang
Qiong
Q
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Huang
Jiaqiang
J
Li
Wen Qing
WQ
Cavinato
Tiziana
T
Keller
Jonathan R
JR
Durum
Scott K
SK
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation; D005822:Genetic Vectors / Q000235:genetics; D053699:Interleukin-7 Receptor alpha Subunit / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000502:physiology; D053651:Receptors, Interleukin-9 / Q000235:genetics / Q000502:physiology; D011981:Receptors, Prolactin / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*
D053699:Interleukin-7 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019948:Receptors, Interleukin-4; D053651:Receptors, Interleukin-9; D011981:Receptors, Prolactin; D011993:Recombinant Fusion Proteins