Trypanosama cruzi INFECTION MODULATES DENDRITIC CELLS MATURATION, MHC CLASS II EXPRESSION AND T CELL PRIMING IN A STRAIN-SPECIFIC MANNER.

ALBA SOTO CATALINA, MIRKIN GERARDO, SOLANA MA. ELISA, FERNANDEZ ESPINOSA D, GONZALEZ-CAPPA STELLA M.

Buenos Aires, Argentina

Simposio; International Symposium on Dendritic Cells And Immunotherapy.; 2002

Maestria en Biología Molecular Médica, Universidad de Buenos Aires

Since dendritic cells (DC) represent de most potent APC for priming naïve T cells, they should play an important role in the elicitation of immune responses against Trypanosoma cruzi. We evaluated, on splenic DC isolated from mice infected with two T.cruzi strains with opposite biological behavior: the expression of MHCII and costimulatory molecules, the state of maturation and the ability to prime in vitro allogeneic T cells. Cell cytometry analysis showed that acute infection with the low virulence T.cruzi strain did not alter, but the high virulence strain down-regulated, the expression of MHCIImolecules. When the expression of CD80, CD86, CD40 and CD24 costimulatory molecules was evaluated, we observed that infection with both T.cruzi strains down-regulated the expression of CD86 molecules. After 12 hours of culture, splenic DC isolated from high virulence strain infected mice formed lower homotypic clusters (a close correlate to their maturation sate) than DC from mice infected with the low virulence strain. Next, we performed a mixed lymphocyte reaction using irradiated DC from infected and control C3H/HeNk mice as stimulators and purified CD4 and CD8 T cells from C57Bl/6b mice as responders. Both allogeneic T cells subsets co-cultured with DC from control and low virulence strain infected mice readily proliferated, whereas those cocultured with DC from the high virulence strain infected mice were unresponsive. The low expression of MHCII molecules and cluster formation might indicate that infection with the virulent strain induces maturation abnormalities of DC. Moreover, DC obtained from mice infected with this strain fail to induce in vitro priming of alloreactive T cells reflecting alterations of ag-presenting function. This results show for the first time that T.cruzi infection affects biological properties of DC in vivo and that  modulation of DC function is accomplished in a strain-specific manner since only the high virulence strain disminishes on DC´s their T cell activating  capacity.