F-022. Ability of Vaginal Dendritic Cells to Induce Mucosal Immunity against Candida albicans in a Rat Model of Vaginitis

F. De Bernardis1, S. Arancia1, R. Lucciarini2, M. Boccanera1, C. Amantini2, S. Graziani1, A. Cassone1, G. Santoni2;
1Istituto Superiore di Sanita', Rome, ITALY, 2Univ. of Camerino, Camerino, ITALY.

Vaginal candidiadis is a common disease affecting a large proportion of women with some of them affected by recurrent often intractable forms of the disease. However the mechanisms of pathogenesis of this frequent disease remain to be still elucidated. To study the host response against vaginal candidiasis we have long employed a rat model of vaginal infection. In this model the protection is associated with the presence of protective antibodies against Candida costituents in the vaginal fluids and the increased number of activated lymphocytes in the vaginal mucosa. We have demonstrated that CD4+Tcell were essential for protection but also that other cellular types were probably involved. In this study we analyzed the phenotype of vaginal dendritic cells (VDCs), their antigenic presentation and activation of T-cell cytokine secretion and their protective role against Candida albicans vaginitis. VDCs were found in the vaginal mucosa on both non-infected and Candida-infected rats by immunohistochemical analysis using the OX 62 Mab. The number of OX62+ VDCs was significantly higher in the vagina of Candida- infected rats. VDCs from infected rats, but not from uninfected rats, released large amount of interleukin (IL)-12 and tumor necrosis factor alpha, stimulate naïve CD4+ T cells to proliferate and to release cytokines, including gamma interferon, IL-2, IL-6, and Il-10. Adoptive transfer of highly purified OX 62+ VDCs from C. albicans infected rats induced 50% reduction of vaginal Candida colonization compared with that in rats receiving naïve VDCs. Then, to demonstrate that the VDCs-mediated protection was associated to their ability to rapidly home to the vagina, we performed migration experiments using carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled VDCs. Forty-eight hours after adoptive transfer comparable numbers of OX 62+ CSFE-VDCs migrated to the vaginal mucosa and lymph nodes. These results indicate that adoptively transferred VDCs from C. albicans infected rats can rapidly migrate to the vagina and draining lymph nodes and protected non infected rats from Candida vaginitis.