INVESTIGADORES
BERGUER Paula Mercedes
congresos y reuniones científicas
Título:
Omp19 co-administered as adjuvant induces antigen cross-presentation and triggers CD8 T cells responses in vivo.
Autor/es:
CORIA, LORENA; IBÁÑEZ, ANDRÉS; BERGUER, PAULA; BARRIONUEVO, PAULA; GIAMBARTALOMEI, GUILLERMO; CASSATARO, JULIANA
Lugar:
Seattle, WA, USA
Reunión:
Simposio; Keystone Symposia, Immunological Mechanisms of Vaccination; 2010
Resumen:
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Previously, we have demonstrated that the protein moiety of Omp19 from Brucella spp.(U-Omp19) has adjuvant properties and could be
used as a Th1 adjuvant that facilitates antigen (Ag)
cross-presentation and induces IFN-γ producing CD8+ T cells. Given
the capacity of antigen presenting cells (APCs) to modulate immune responses,
in the present study we investigated if APCs are involved in the ability of U-Omp19
to stimulate a specific CD8 T cell response. To assess this, purified dendritic
cells (DCs) from spleen of C57BL/6 mice were treated with ovoalbumin (OVA)
alone or plus U-Omp19 or LPS as positive control and then co-cultivated with
OTI CD8+ T cells. We evaluated the induction of IFN-γ producing T cells by intracellular IFN-γ staining and degranulation of cytotoxic T
cells by CD107a expression on the membrane. A higher percentage
of IFN-γ producing T CD8 (32.36%) and cytotoxic T
cells (14.06%) was induced when DCs were stimulated with OVA+U-Omp19 compared
to T cells co-cultivated with DCs pulsed with OVA alone (23.42% and 8.98%
respectively). These results suggested that U-Omp19 can act directly on DCs to enhance
T cell responses. Therefore, we evaluated if Omp19 has a direct effect on APCs that could enhance the Ag internalization
and presentation to T cells. To this end, purified DCs from spleen mice were
pulsed in vitro with OVA-FITC alone
or OVA-FITC+U-Omp19 or LPS as positive control. DCs pulsed with OVA-FITC+U-Omp19
showed a greatly increase in Ag internalization compared with OVA alone (MFI
367.88±19.1 vs. 15.29±1.8). We have also found that U-Omp19 increased OVA
internalization by J774 macrophage cell line and by A20J B-lymphoma cell line at
different times. These results indicate that U-Omp19 increases the Ag capture
by immature DCs, macrophages and B lymphocytes. In conclusion, U-Omp19 as adjuvant increases the amount
of internalized Ag in APCs. This capacity would lead the improved T CD8 and CTL immune responses observed when
U-Omp19 is co-administered with the Ag.
