Ablation of core fucosylation attenuates the signal transduction via T cell receptor to suppress the T cell development

Abstract

Precise glycosylation plays a crucial and distinctive role in thymic T cell development. The core fucosylation is dramatically up-regulated at the transition from CD4^-CD8^- (DN) to CD4⁺CD8⁺ (DP) in the thymic development. Ablation of core fucosylation in T cells did reduce the size of the thymus due to a significant loss of CD4⁺ SP, CD8⁺ SP and DP thymocytes in core fucosyltransferase (Fut8) knockout (Fut8^-/-) mice. T cell receptors (TCRs) are heavily core fucosylated glycoproteins. Loss of core fucosylation of TCR contributed to the reduced phosphorylation of ZAP70 (pZAP70) in Fut8^-/- DP cells was observed. Compare to the Fut8^+/+OT-II DP thymocytes, pZAP70 was significantly reduced in Fut8^-/- OT-II DP thymocytes with OVA_323-339 stimulation. Also, the pZAP70 of Fut8^+/+OT-I DP thymocytes with OVA_257-264 stimulation was remarkably attenuated by treatment of the fucosidase. Upon anti-CD3/CD28 Abs stimulation, the increased apoptosis was found in Fut8^-/- thymocytes compared with Fut8^+/+ thymocytes. Moreover, the TCR^hiCD69^hi (post-positive selection thymocytes) was markedly depleted in the Fut8^-/- thymus without any stimulation. The expression of CD5 was significantly down-regulated on the DP cells in the Fut8^-/- thymus. Our results therefore demonstrate that ablation of core fucosylation results in the abnormal T cell development due to the attenuated signaling via TCR.

Keywords: Core fucosylation; Signal transduction; T cell receptor; Thymic development.