Seminal Plasma Modulates Dendritic Cell Function Favoring the Generation of CD25+/FOXP3+ T-cells

MERLOTTI IPPÓLITO, ANTONELLA; RUIZ, MARÍA JULIA; ERRA DÍAZ, FERNANDO; DANTAS, EZEQUIEL; VARESE, AUGUSTO; DUETTE, GABRIEL; PEREYRA, PEHUÉN; ERNST, GLENDA; GEFFNER, JORGE; SABATTE, JUAN

Ciudad del Cabo

Congreso; HIV Research for Prevention Conference; 2014

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 pro-inflammatory cytokines and favoring the induction of CD25 + /FOXP3 + T cells. In this way, we speculate that SP might modulate the adaptive immune response against sexual transmitted pathogens.