Costimulatory action of glycoinositolphospholipids from Trypanosoma cruzi: increased interleukin 2 secretion and induction of nuclear translocation of the nuclear factor of activated T cells 1.
The effects of the glycoinositolphospholipids (GIPLs) fromTrypanosoma cruzi on T lymphocyte activation were investigated in a mouse T cell hybridoma (DO-11.10). Purified GIPLs from T. cruzi strains Y and G markedly increased IL-2 mRNA transcripts and IL-2 secretion induced by mitogenic anti-CD3 and anti-Thy1 mAbs. This costimulatory function was also revealed by the induction of IL-2 secretion after the simultaneous addition of the T. cruzi GIPLs and either the calcium ionophore A23187 or phorbol ester. The capacity of the GIPL molecule to induce an increase in cytoplasmic calcium levels was also demonstrated. After exposure of T cell hybridoma to GIPL, the nuclear transcription factor NFAT1 became partially dephosphorylated, and its nuclear localization was demonstrated both in the T cell hybridoma and in Balb/c CD3(+) cells. These results demonstrate that T. cruzi GIPL molecules are capable of signaling to T cells and therefore could be valuable tools for the study of T cell activation, besides playing a potential role in subverting the T lymphocyte immune response during T. cruzi infection.
Bellio
M
M
Instituto de Microbiologia, Departamento de Histologia e Embriologia, Instituto de Biofísica Carlos Chagas F degrees, Universidade Federal do Rio de Janeiro, 21.941-590 Rio de Janeiro, RJ, Brazil. belliom@acd.ufrj.br
Liveira
A C
AC
Mermelstein
C S
CS
Capella
M A
MA
Viola
J P
JP
Levraud
J P
JP
Dosreis
G A
GA
Previato
J O
JO
Mendonça-Previato
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006017:Glycolipids / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010743:Phospholipids / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D006017:Glycolipids; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010743:Phospholipids; D014157:Transcription Factors; C115336:glycoinositolphospholipid, Trypanosoma; D000001:Calcimycin