Transferrin is required for early T-cell differentiation.
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.
Macedo
M Fatima
MF
Division of Human Genetics and Genetic Disorders, Iron and the Immune System Laboratory, Institute for Molecular and Cell Biology, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. mdesousa@ibmc.up.pt
de Sousa
Maria
M
Ned
Renee M
RM
Mascarenhas
Claudia
C
Andrews
Nancy C
NC
Correia-Neves
Margarida
M
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D006454:Hemoglobins / Q000378:metabolism; D007501:Iron / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011990:Receptors, Transferrin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014168:Transferrin / Q000276:immunology*
D006454:Hemoglobins; D011990:Receptors, Transferrin; D014168:Transferrin; D007501:Iron