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Instituto de Microbiologia Prof. Paulo de Goes,
* Departamento de Histologia e Embriologia, ICB,
Instituto de Biofísica Carlos Chagas F°, Universidade Federal do Rio de Janeiro, 21.941590 Rio de Janeiro, RJ, Brazil;
Programa de Medicina Experimental, Instituto Nacional do Cancer, Rio de Janeiro, RJ, Brazil; and
§ Unité INSERM U 277, Institut Pasteur, 75724 Paris Cedex 15, France
1Correspondence: Depto. de Imunologia/Instituto de Microbiologia Prof. Paulo de Goes, CCS Bl. I - 2° andarSala: I2053, UFRJ -Cidade Universitaria, CEP: 21941590 Ilha do Fundao, Rio de Janeiro, RJ. Brazil. E-mail: belliom{at}acd.ufrj.br
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., Oliveira,A.-C. S. C., Mermelstein, C. S., Capella, M. A. M., Viola, J. P. B., Levraud, J.-P., Dosreis, G. A., Previato, J. O., Mendonça-Previato, L. 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.
Key Words: T cell activation ceramide costimulation Chagas' disease cytosolic calcium
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