Glycobiology, 2002, Vol. 12, No. 1 25-32
© 2002 Oxford University Press
Trypanosoma cruzi surface mucin TcMuc-e2 expressed on higher eukaryotic cells induces human T cell anergy, which is reversible
2Instituto de Ciencias Básicas y Medicina Experimental,Hospital Italiano de Buenos Aires, Gascón 450, (1181) Buenos Aires, Argentina; 3Instituto de Investigaciones Biotecnológicas, Instituto Tecnológico de Chascomús CONICET, Universidad Nacional de General San Martín, Pcia. de Buenos Aires, Argentina; 4Laboratory of Molecular Pathology, Hospital Italiano de Buenos Aires, Gascón 450, (1181) Buenos Aires, Argentina; 5Laboratory of Clinical Immunology, Hospital Italiano de Buenos Aires, Gascón 450, (1181) Buenos Aires, Argentina; and 6Laboratory of Immunogenetics from Hospital Italiano de Buenos Aires, Gascón 450, (1181) Buenos Aires, Argentina
Chagas’ disease is a chronic, debilitating, multisystemic disorder that affects millions of people in Latin America. The protozoan parasite Trypanosoma cruzi, the etiological agent of Chagas’ disease, has a large number of O-glycosylated Thr/Ser/Pro-rich mucin molecules on its surface (TcMuc). These mucins are the main acceptors of sialic acid and have been suggested to play a role on various host–parasite interactions, such as adhesion to macrophages, protection from complement lysis, and immunomodulation of the immune response mounted by the host. To observe the immunologic effect obtained by the heterologous expression of a TcMuc gene in higher eukaryotic cells exposed to xenogeneic lymphocytes, we developed a strategy based on the transfection of a known T. cruzi mucin gene (TcMuc-e2) into Vero cells. In contrast to the brisk proliferation and activation of human lymphocytes observed at 3, 4, and 5 days induced by normal Vero cells, neither proliferation nor signicant activation of human lymphocytes was observed with TcMuc-e2-transfected Vero cells. This TcMuc-e2 mucin-induced suppression of T cell response can be reversed by the addition of exogenous IL-2. In addition it was demonstrated that the immunosuppressive reaction was not related to the induction of an important degree of apoptosis in human lymphocytes. Posttranslational modification are required for the inhibitory effect that TcMuc-e2 exerts when transfected to Vero cells. O-glycosylation and sialylation are required to obtain the immunomodulatory effect as assessed by O-sialoglycoprotease and neuraminidase treatments. These results are consistent with other studies showing that surface glycoconjugates from T. cruzi and mammalian cells can induce an inhibition of the immune response.
1 To whom correspondence should be addressed
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. Heise, D. Singh, H. van der Wel, S. O Sassi, J. M Johnson, C. L Feasley, C. M Koeller, J. O Previato, L. Mendonca-Previato, and C. M West Molecular analysis of a UDP-GlcNAc:polypeptide {alpha}-N-acetylglucosaminyltransferase implicated in the initiation of mucin-type O-glycosylation in Trypanosoma cruzi Glycobiology, August 1, 2009; 19(8): 918 - 933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Carlos, H. F. Dong, O. M. Z. Howard, J. J. Oppenheim, F.-G. Hanisch, and O. J. Finn Human Tumor Antigen MUC1 Is Chemotactic for Immature Dendritic Cells and Elicits Maturation but Does Not Promote Th1 Type Immunity J. Immunol., August 1, 2005; 175(3): 1628 - 1635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Alcaide and M. Fresno The Trypanosoma cruzi membrane mucin AgC10 inhibits T cell activation and IL-2 transcription through L-selectin Int. Immunol., October 1, 2004; 16(10): 1365 - 1375. [Abstract] [Full Text] [PDF]
|
|