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Figure 1: Model depicting the inhibitory effect of Trypanosoma cruzi sialoglycoproteins on T cell activation. Schematic diagram showing the sialylation of O-linked oligosaccharides of mucin-derived trypomastigotes mediated by the surface-associated T. cruzi parasite trans-sialidase. The parasite trans-sialidase, which can also be shed into the bloodstream or tissue interstitium after cleavage of its glycosylphosphatidylinositol (GPI) anchor by the action of a phosphatidylinositol-phospholipase C, transfers sialic-acid residues from host glycoconjugates to parasite mucins. It has been demonstrated in other studies that the T. cruzi parasite-derived mucins bind to mammalian host cell receptors such as the acid-binding Ig-like lectin receptor Siglec-E (CD33) and undermine host defence mechanisms. In CD4+ T cells, we showed that the Siglec-E receptor inhibits the mitogenic responses upon T cell receptor stimulation. The initiation of the G1 to S transition during antigenic/mitogenic T cell expansion is mediated by cyclin D and cyclin-dependent kinases CDK2 or CDK6, which are induced and together initiate the G1/S transition. We have shown that the G1/S transition is significantly inhibited by the sialyl terminal residues of T. cruzi mucins and we propose that this phenomenon is mediated by its interaction with the Siglec-E receptor. The interaction of CD4+ T cells with the sialylated form of the parasite mucin leads to induction of p27/Kip1, a member of the family of CDK inhibitors that negatively regulate the G1 to S transition, so damping T cell-mediated immune responses by inducing T cell cycle arrest.