Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes

L Van Overtvelt, M Andrieu, V. Verhasselt, F Connan, J Choppin, S. Vercruysse, M Goldman, A Hosmalin, B Vray

Research output: Contribution to journalArticle

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Abstract

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-1(514-522) 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-gamma 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.

Original languageEnglish
Pages (from-to)1135-1144
Number of pages10
JournalInternational Immunology
Volume14
Issue number10
Publication statusPublished - Oct 2002

Cite this

Van Overtvelt, L ; Andrieu, M ; Verhasselt, V. ; Connan, F ; Choppin, J ; Vercruysse, S. ; Goldman, M ; Hosmalin, A ; Vray, B. / Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes. In: International Immunology. 2002 ; Vol. 14, No. 10. pp. 1135-1144.
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title = "Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes",
abstract = "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-1(514-522) 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-gamma 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-gamma ELISPOT, trypomastigote surface antigen, TUMOR-NECROSIS-FACTOR, HERPES-SIMPLEX VIRUS, CHAGAS-DISEASE, APOPTOTIC CELLS, BACTERIAL LIPOPOLYSACCHARIDE, COSTIMULATORY MOLECULES, IMMUNE-SYSTEM, ACUTE-PHASE, INFECTION, MICE",
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Van Overtvelt, L, Andrieu, M, Verhasselt, V, Connan, F, Choppin, J, Vercruysse, S, Goldman, M, Hosmalin, A & Vray, B 2002, 'Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes' International Immunology, vol. 14, no. 10, pp. 1135-1144.

Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes. / Van Overtvelt, L; Andrieu, M; Verhasselt, V.; Connan, F; Choppin, J; Vercruysse, S.; Goldman, M; Hosmalin, A; Vray, B.

In: International Immunology, Vol. 14, No. 10, 10.2002, p. 1135-1144.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8(+) T lymphocytes

AU - Van Overtvelt, L

AU - Andrieu, M

AU - Verhasselt, V.

AU - Connan, F

AU - Choppin, J

AU - Vercruysse, S.

AU - Goldman, M

AU - Hosmalin, A

AU - Vray, B

PY - 2002/10

Y1 - 2002/10

N2 - 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-1(514-522) 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-gamma 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.

AB - 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-1(514-522) 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-gamma 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.

KW - cytotoxicity

KW - dendritic cell maturation

KW - immune escape

KW - IFN-gamma ELISPOT

KW - trypomastigote surface antigen

KW - TUMOR-NECROSIS-FACTOR

KW - HERPES-SIMPLEX VIRUS

KW - CHAGAS-DISEASE

KW - APOPTOTIC CELLS

KW - BACTERIAL LIPOPOLYSACCHARIDE

KW - COSTIMULATORY MOLECULES

KW - IMMUNE-SYSTEM

KW - ACUTE-PHASE

KW - INFECTION

KW - MICE

M3 - Article

VL - 14

SP - 1135

EP - 1144

JO - International Immunology

JF - International Immunology

SN - 0953-8178

IS - 10

ER -