Role of the intracellular domain of IL-7 receptor in T cell development

J Immunol. 2007 Jan 1;178(1):228-34. doi: 10.4049/jimmunol.178.1.228.

Abstract

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Differentiation / genetics
  • Cell Lineage / genetics
  • Cell Proliferation
  • Genetic Vectors / genetics
  • Interleukin-7 Receptor alpha Subunit / genetics
  • Interleukin-7 Receptor alpha Subunit / physiology*
  • Mice
  • Mice, Mutant Strains
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / physiology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / physiology
  • Receptors, Interleukin-4 / genetics
  • Receptors, Interleukin-4 / physiology
  • Receptors, Interleukin-9 / genetics
  • Receptors, Interleukin-9 / physiology
  • Receptors, Prolactin / genetics
  • Receptors, Prolactin / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / growth & development
  • Thymus Gland / immunology*

Substances

  • Interleukin-7 Receptor alpha Subunit
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Interleukin-4
  • Receptors, Interleukin-9
  • Receptors, Prolactin
  • Recombinant Fusion Proteins