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International Immunology Advance Access originally published online on August 16, 2004
International Immunology 2004 16(10):1365-1375; doi:10.1093/intimm/dxh138
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© 2004 The Japanese Society for Immunology

The Trypanosoma cruzi membrane mucin AgC10 inhibits T cell activation and IL-2 transcription through L-selectin

Pilar Alcaide and Manuel Fresno

Centro de Biología Molecular (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, Madrid, 28049 Spain

Correspondence to: M. Fresno; E-mail: Mfresno{at}cbm.uam.es

Trypanosoma cruzi infection is associated with a severe T cell unresponsiveness to antigens and mitogens characterized by a decreased IL-2 synthesis and by nitric oxide (NO) production. Although spleen cell unresponsiveness to ConA was less severe in infected IFN-{gamma}R–/– or inducible nitric oxide synthase (iNOS)–/– mice than in control littermates, IL-2 inhibition was as severely impaired. Ag C10, a T. cruzi mucin, inhibited T cell proliferation as well as IL-2 secretion and IL-2 mRNA induction in response to mitogens and to anti-CD3. This effect took place at the transcriptional level since Ag C10 was able to inhibit IL-2 promoter-driven transcription. Moreover, the transcription of reporter genes controlled by CD28RE, NFAT or AP-1, but not by NF-{kappa}B sites, were inhibited by AgC10 to different degrees, although the greatest effect was observed for NFAT. In agreement with that, overexpression of NFAT significantly reverted Ag C10 inhibition of IL-2 transcription. AgC10 also inhibited early steps of T cell activation as tyrosine phosphorylation of the tyrosine kinase ZAP-70 and the adapter protein SLP-76. AgC10 binds to T cell surface through CD62L, and antibodies to CD62L inhibited T cell proliferation and IL-2 secretion and transcription as efficiently as AgC10. Indeed, AgC10 did not inhibit activation by T cells from CD62L-deficient mice (Sell–/–). Our results suggest that Ag C10, through binding to L-selectin, was able to inhibit different activation pathways that lead to inhibition of IL-2 secretion and T cell proliferation. This was independent of NO and IFN-{gamma}.

Keywords: cell surface molecules, cytokines, T lymphocytes, parasitic protozoan

Transmitting editor: C. Terhorst


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