A transgenic T cell receptor restores thymocyte differentiation in interleukin-7 receptor alpha chain-deficient mice

Eur J Immunol. 1997 Jan;27(1):100-4. doi: 10.1002/eji.1830270115.

Abstract

Interleukin-7 (IL-7) receptor alpha chain-deficient (IL-7R alpha-/-) mice have severely depleted lymphocyte populations and thymocyte development is arrested at the double-negative (DN) stage. We show that thymocyte development in these mice can be reconstituted by the introduction of a transgenic T cell receptor (TCR), implying that one function of the IL-7R alpha chain is to initiate TCR gene rearrangement. Expression of the recombinase-activating genes RAG1 and RAG2 was greatly reduced in the IL-7R alpha-/- thymuses, and in DN thymocytes from the TCR transgenic IL-7R alpha-/- mice, but was restored in double-positive thymocytes from the TCR transgenic IL-7R alpha-/- mice. These data suggest that the IL-7R alpha chain controls RAG expression and initiation of TCR beta chain VDJ rearrangement in DN cells. In contrast, once cells have progressed beyond the DN stage of development the IL-7R alpha chain becomes no longer essential for RAG expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • DNA-Binding Proteins
  • Gene Expression
  • Gene Rearrangement, T-Lymphocyte*
  • Hematopoiesis
  • Homeodomain Proteins*
  • Interleukin-7 / physiology*
  • Mice
  • Mice, Transgenic
  • Proteins / genetics
  • RNA, Messenger / genetics
  • Receptors, Antigen, T-Cell / physiology*
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-7
  • Signal Transduction
  • T-Lymphocyte Subsets / cytology*
  • Thymus Gland / cytology*
  • Thymus Gland / embryology

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Interleukin-7
  • Proteins
  • RNA, Messenger
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin
  • Receptors, Interleukin-7
  • V(D)J recombination activating protein 2
  • RAG-1 protein