Congresos y reuniones científicas
Título:
Poor cytotoxic response in leukocyte-specific protein-1 deficient mice is associated with a reduced cross-presentation by CD+ DCS.
Autor/es:
ACLAND,R; ZACCA, E; PISTORESI, MC; MALETTO, B; MORÓN, G
Reunión:
Congreso; LXII Reunión de la Sociedad Argentina de Inmunología.; 2014
Institución organizadora:
Sociedad Argentina de Inmunología.
Resumen:
The leukocyte-specific protein 1 (LSP1), is a 52-kDa cytoplasmic
F-actin binding phosphoprotein expressed in leukocytes
and endothelial cells that regulates cytoskeleton thus cell motility
and polarization. It has been reported that human and murine
LSP1-/- dendritic cells (DCs), infected with HIV show decreased
proteasome degradation and altered intracellular trafficking of
virus. This unexpected finding suggests a putative role of LSP1 in
antigen cross-presentation in DCs. To investigate this hypothesis,
we measured the ability of LSP1-/- DCs pulsed with an exogenous
antigen (ovalbumin, OVA) plus polyuridilic acid (PU, a TLR7 ligand)
to induce cytotoxic response. We found that wild-type (WT) mice
that received the OVA/PU-pulsed LSP1-/- DCs had a lower CTL
response (30±8% of specific lysis) compared to mice transferred
with OVA/PU-pulsed WT DCs (64±3%, p<0.01). WT and LSP1-
/- splenocytes or BMDCs showed no differences in OVA uptake.
Using a H2-Kb-restricted OVA257-264 epitope CD8+ T cell hybridoma,
we found that LSP1-/- CD8a+ DCs have a lower ability to activate
CD8 T cells when pulsed with whole OVA in comparison to WT
CD8a+ DCs, but the same ability when DCs are pulsed with the
peptide OVA256-264, revealing a role for LSP1 in antigen crosspresentation.
We have previously showed no differences in DC
and other leukocyte content in the spleen of WT vs LSP1-/- mice as
well as a similar ability in DCs to mature upon TLR7 stimulation.
Furthermore, we analyzed the ability of LSP1-/- DCs to migrate to
lymphoid tissues. By flow cytometry we observed a delayed DC
arrival to draining lymph nodes after subcutaneous injection of
LSP1-/-DCs into wt mice, compared to injected WT DCs (p<0,001
24h, ns 48hs post injection) showing that LSP1-/- DCs have an
impaired migratory activity compared to WT mice. In conclusion,
LSP1 is involved in antigen cross-presentation and cell migration in
DCs in a way that its lack results in decreased cytotoxic responses.