Transferrin is required for early T-cell differentiation

M Macedo

Maria de Sousa

Renee Ned

Claudia Mascarenhas

Nancy Andrews

Margarida Correia-Neves

^{Division of Human Genetics and Genetic Disorders, Iron and the Immune System Laboratory, Institute for Molecular and Cell Biology (IBMC), Oporto, Portugal}

^{Microbiology and Immunology of Infection, Institute for Molecular and Cell Biology (IBMC), Oporto, Portugal}

^{Molecular Pathology and Immunology, Instituto de Ciências Biomédicas Abel Salazar, Oporto, Portugal}

^{Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Boston, MA, USA}

^{Division of Medical Sciences, Harvard Medical School, Boston MA, USA}

^{Howard Hughes Medical Institute, Boston, MA, USA}

^{Instituto Superior de Saúde do Alto Ave (ISAVE), Fontarcada, Portugalv}

Correspondence: Dr M. de Sousa, Molecular Immunology, Institute for Molecular and Cell Biology (IBMC), room #2.58, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. E-mail: tp.pu.cmbi@asuosedm

Received 2004 Apr 2; Revised 2004 May 3; Accepted 2004 May 5.

Abstract

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^{) mice to investigate the possible involvement of transferrin in T lymphocyte differentiation}in vivo. The absolute number of thymocytes was substantially reduced in Trf^{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.

Keywords: transferrin, transferrin receptor, iron, T-cell differentiation, thymus

Abstract

Data represent means and their standard deviations.

Acknowledgments

M.F. Macedo has a PhD fellowship, as part of the G.A.B.B.A. Program, funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal): Praxis XXI/BD/13685/97. This work was financed in part by FCT: POCTI/1999/32986, Fundação Calouste Gulbenkian: GULBHEM project/2002 (Portugal), the American Portuguese Biomedical Research Fund (APBRF, USA) and NIH HL51057 to N.C. Andrews. N.C. Andrews is an Associate Investigator of the Howard Hughes Medical Institute. We thank Angel Custodio for developing the Trf^{mice genotyping protocol, Graça Porto and Eugénia Cruz for the help in assessing the anaemic status of the mice. We are also grateful to M. Fátima Martins, Célia Lopes and M. Júlia Reis for the excellent technical assistance.}

Acknowledgments

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