Alteration of intracellular calcium flux and impairment of nuclear factor-AT translocation in T cells during acute Toxoplasma gondii infection in mice.
Down-regulation of host immune response to Toxoplasma gondii is associated with the expression of specific cytokines, in particular IL-10, and the induction of CD4+ T cell anergy. In the present study we report that the expression of both CD4 and CD2 antigen is down-regulated during the acute phase of infection. A decrease in the expression of CD2 was apparent during the acute phase of T. gondii infection in three genetically distinct strains of mice, CBA/J, C57BL/6, and BALB/c. The lymphoproliferative response induced by cross-linked anti-CD3 mAb or by Con A was markedly depressed. This suppressed response was associated with a reduction in the influx of Ca2+. We have examined whether lymphocytes from T. gondii mice maintain NF-AT transcription factors in the nucleus where they participate in the Ca2+-dependent induction of genes required for lymphocyte activation and proliferation. Immunofluorescence with confocal microscopy using an Ab to NF-ATc demonstrates a decrease in translocation of NF-ATc in T lymphocytes from acutely infected mice. Together, these results suggest that the defect in T cell expansion that occurs during acute murine toxoplasmosis is related to reduced activity of NF-AT, a calcium-dependent transcription factor required for T cell proliferation.
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Department of Medicine and Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA. s.haque@medecine.univ-mrs.fr
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D000208:Acute Disease; D000818:Animals; D001692:Biological Transport; D018801:CD2 Antigens / Q000096:biosynthesis* / Q000235:genetics; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020013:Calcium Signaling; D002467:Cell Nucleus / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004198:Disease Susceptibility; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D018801:CD2 Antigens; D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014157:Transcription Factors; D003208:Concanavalin A