International Immunology, Vol. 14, No. 10, pp. 1135-1144,
October 2002
© 2002 Japanese Society for Immunology
Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8+ T lymphocytes
1 Laboratoire d’Immunologie Expérimentale (CP 615), Faculté de Médecine, and Laboratoire de Parasitologie, Faculté des Sciences, Université Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium 2 Laboratoire d’Immunologie des Pathologies Infectieuses et Tumorales, INSERM U445, Département d’Immunologie, ICGM, 27 rue du Faubourg St-Jacques, 75014 Paris, France
Correspondence to: B. Vray; E-mail: bvray{at}ulb.ac.be
Transmitting editor: G. Trinchieri
Trypanosoma cruzi, the etiological agent of Chagas’ disease, may persist for many years in its mammalian host. This suggests escape from the immune response and particularly a suboptimal CD8+ T cell response, since these cells are involved in infection control. In this report, we show that T. cruzi inhibits the lipopolysaccharide (LPS)-induced up-regulation of MHC class I molecules at the surface of human dendritic cells (DC). To further investigate the functional consequences of this inhibition, a trypomastigote surface antigen-derived peptide (TSA-1514–522 peptide) was selected for its stable binding to HLA-A*0201 molecules and used to generate a primary T. cruzi-specific human CD8+ T cell line in vitro. We observed that DC infected with T. cruzi or treated with T. cruzi-conditioned medium (TCM) had a weaker capacity to present this peptide to the specific CD8+ T cell line as shown in an IFN-
ELISPOT assay. Interestingly, T. cruzi or TCM also reduced the antigen presentation capacity of DC to CD8+ T cell lines specific for the influenza virus M58–66 or HIV RT476–484 epitopes. This dysfunction appears to be linked essentially to reduced MHC class I molecule expression since the stimulation of the RT476–484 peptide-specific CD8+ T cell line was shown to depend mainly on the MHC class I–TCR interaction and not on the co-stimulatory signals which, however, were also inhibited by T. cruzi. This impairment of DC function may represent a novel mechanism reducing in vivo the host’s ability to combat efficiently T. cruzi infection.
Keywords: cytotoxicity, dendritic cell maturation, immune escape, IFN- ELISPOT, trypomastigote surface antigen
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