Transferrin is required for early T-cell differentiation

Immunology. 2004 Aug;112(4):543-9. doi: 10.1111/j.1365-2567.2004.01915.x.


Transferrin, the major plasma iron carrier, mediates iron entry into cells through interaction with its receptor. Several in vitro studies have demonstrated that transferrin plays an essential role in lymphocyte division, a role attributed to its iron transport function. In the present study we used hypotransferrinaemic (Trf(hpx/hpx)) mice to investigate the possible involvement of transferrin in T lymphocyte differentiation in vivo. The absolute number of thymocytes was substantially reduced in Trf(hpx/hpx) mice, a result that could not be attributed to increased apoptosis. Moreover, the proportions of the four major thymic subpopulations were maintained and the percentage of dividing cells was not reduced. A leaky block in the differentiation of CD4(-) CD8(-) CD3(-) CD44(-) CD25(+) (TN3) into CD4(-) CD8(-) CD3(-) CD44(-) CD25(-) (TN4) cells was observed. In addition, a similar impairment of early thymocyte differentiation was observed in mice with reduced levels of transferrin receptor. The present study demonstrates, for the first time, that transferrin itself or a pathway triggered by the interaction of transferrin with its receptor is essential for normal early T-cell differentiation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cell Differentiation / immunology
  • Cell Division / immunology
  • Hemoglobins / metabolism
  • Iron / blood
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Transferrin / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology
  • Transferrin / immunology*


  • Hemoglobins
  • Receptors, Transferrin
  • Transferrin
  • Iron