Proliferating CD4+ T cells undergo immediate growth arrest upon cessation of TCR signaling in vivo

J Immunol. 2008 Jan 1;180(1):156-62. doi: 10.4049/jimmunol.180.1.156.

Abstract

To investigate the role of TCR signaling in the exit of CD4+ T cells from cell cycle, we took advantage of a low frequency TEa T cell adoptive transfer technique as well as the Y-Ae mAb to interrupt Ag/MHC recognition before the completion of clonal expansion. Termination of TCR signaling after 36 h of Ag exposure caused an immediate reduction in cell size and deceleration of G1->SG2M phase cell cycle progression. As a consequence, clonal expansion in the absence of durable TCR signaling decreased by two-thirds. Thus, CD4+ T cells scan for the presence Ag throughout their clonal expansion response, and continuously adjust their rate of cell growth and G1->S phase transition to match their intensity of TCR signaling.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD28 Antigens / analysis
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Cycle
  • Cell Division*
  • Cell Proliferation
  • Ligands
  • Lymphocyte Activation*
  • Major Histocompatibility Complex / immunology
  • Mice
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction

Substances

  • Antibodies, Monoclonal
  • CD28 Antigens
  • Ligands
  • Receptors, Antigen, T-Cell