Proliferating cells require iron and, therefore, express the transferrin receptor (CD71) that mediates cellular iron uptake. Cycling thymocytes, which have the CD4−8−3−, CD4−8+3−, or CD4+8+3− phenotypes, also express CD71. The importance of CD71-mediated iron uptake for proliferation and maturation of thymocytes was studied using fetal thymus organ cultures at day 14 of gestation and treating them for 7 days with a CD71 monoclonal antibody (mAb). The intracellular iron deficiency caused by this treatment, inhibits both proliferation and maturation of the thymocytes. Cell recovery was reduced by 60%, but cells still expanded tenfold during the culture. Remarkably, the final maturation of αβ T cells was completely blocked as no thymocytes with low or high CD3/αβTcR expression developed. Moreover, only few cells reached the CD4+8+3− stage of T cell development. CD4−8−3− thymocytes, however, as well as its CD44−25+ subset developed in normal numbers, suggesting that CD44−25+ CD4−8−3− cells, or their immediate progeny, were most vulnerable to CD71 mAb treatment. The development of γδ T cells, which also express CD71, was not affected in these cultures. This suggests that γδ T cells are either less iron-dependent or possess alternative iron-uptake mechanisms. Thus, our observations indicate that CD71 treatment, causing decreased intracellular iron levels, severely inhibits the major proliferation phase from the CD44−25+ CD4−8−3− to the CD4+8+3− cells, and completely abrogates the final maturation of CD4+8+3− cells into αβTcR-expressing cells. In contrast, proliferation and differentiation of the earliest thymic precursors into CD44−25+ CD4−8−3− cells is not affected by CD71 treatment.

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European Journal of Immunology
Department of Immunology

Brekelmans, P., van Soest, P., Leenen, P., & van Ewijk, W. (1994). Inhibition of proliferation and differentiation during early T cell development by anti-transferrin receptor antibody. European Journal of Immunology, 24(11), 2896–2902. doi:10.1002/eji.1830241147