Interleukin-2-dependent autocrine proliferation in T-cell development

Nature. 1989 Nov 2;342(6245):82-5. doi: 10.1038/342082a0.

Abstract

Activated T lymphocytes proliferate in response to interleukin-2 (IL-2), which binds to a specific high-affinity receptor (IL-2R). This consists of at least two noncovalently linked polypeptides, p55/IL-2R alpha (Tac) and p75/IL-2R beta. Both molecules bind IL-2 independently, with low and intermediate affinity respectively, but only IL-2R beta is thought to mediate IL-2 signal transduction. Although IL-2R beta seems to be constitutively expressed on resting T lymphocytes, the growth of these T cells is specifically induced by antigenic triggering by the T-cell receptor (TCR), which then results in the transcription of both IL-2 and IL-2R alpha genes. By contrast, activation of the IL-2/IL-2R pathway in the thymus seems to precede the appearance of the TCR, as IL-2R alpha is expressed on T-cell precursors lacking TCR. The basis for IL-2R expression by immature thymocytes, however, remains largely unknown. We show here that IL-2R alpha-negative T-cell precursors constitutively express IL-2R beta and produce their own IL-2. The IL-2/IL-2R beta interaction on these cells induces the expression of IL-2R alpha, leading to high-affinity IL-2R display and cellular proliferation. We suggest that this IL-2-dependent autocrine pathway of growth stimulation plays a key role in the intrathymic development of mature T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • Gene Expression
  • Humans
  • Interleukin-2 / analysis
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology*
  • Lymphocytes* / immunology*
  • Receptors, Interleukin-2 / immunology*
  • Recombinant Proteins / analysis
  • T-Lymphocytes / immunology*
  • Transcription, Genetic

Substances

  • Antigens, CD
  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Proteins