INBIRS   24491
INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Seminal Plasma Modulates Dendritic Cell Function Favoring the Generation of CD25+/ FOXP3+ T-cells
Autor/es:
A. MERLOTTI; M.J. RUIZ; F. ERRA DÍAZ; E. DANTAS; A. VARESE; G. DUETTE; P. PEREYRA GERBER; G. ERNST; F. REMES LENICOV; J. GEFFNER; J. SABATTÉ
Lugar:
Ciudad del Cabo
Reunión:
Congreso; HIV R4P; 2014
Resumen:
Background: Unprotected sexual intercourse is
the most common mode of HIV-1 transmission being semen the most important
vector for this infection. Dendritic cells (DCs) are abundantly located on
mucosal surfaces and play different roles during HIV infection: promote HIV spread
by boosting CD4+ T cell infection and activate the HIV specific adaptive immune
response. As semen has been shown to promote immune tolerance in different models,
we hypothesize that components present in plasma seminal (SP) might modulate DC
function promoting a tolerogenic immune response. To test this, we study the
ability of complete SP to modulate DC function
and the ability of these cells to induce CD25+/FOXP3+
regulatory T cells.
Methods: SP was obtained from healthy
donors. Monocyte derived DCs were cultured during 24 hs with SP samples
(diluted 1/100) in the absence or presence of LPS (10ng/ml). DC phenotype was
studied by flow cytometry. Cytokine secretion was measured in culture
supernatants by ELISA. After SP treatment, DCs were cultured with allogeneic
CD4+ T cells and the induction of CD25+/FOXP3+ T cells was analyzed by flow cytometry.
Results: We found that SP inhibited IL-12,
IL-6, TNF-alpha and IL-1, but not IL-10 production by LPS stimulated DCs
(percent of inhibition respect to LPS alone: 81.2+/-11.07% p< 0.0001 for
IL-12, 43.45+/-2.87% p< 0.001 for IL-6, 69.8+/-17.31% p< 0.001 for
TNF-alpha, 37.5+/-13.15% p< 0.05 for IL-1, 6.1+/-15.6% p=0.6 for IL-10). SP
also boosted the ability of LPS stimulated DCs to induce CD25+/FOXP3+ T cells (PS+LPS=20,4%
vs LPS alone=6%, p< 0,05). We observed no changes on the expression of
HLA-DR, CD80, CD86, CD83, CD40 and CD1a on immature or LPS-maturated DCs after
incubation with SP.
Conclusions: SP modulates DC function,
inhibiting the secretion of proinflammatory cytokines and favoring the
induction of CD25+/FOXP3+ T cells. In this way, we speculate that SP might
modulate the adaptive