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Figure 4 Vaginal scrapings taken from rats infected with C. albicans showing development from yeast (A. day 0) to mycelial (B. day 7) cells. The smears were stained by the periodic acid Schiff method. Magnification X 200. (Courtesy of Dr. L. Morelli, Lab. Veterinary Medicine. Istituto Superiore di SanitA, Rome, Italy.)

Thus, the study of T-cell activation at the vaginal level remains a key point for understanding local host immunity. In this context, we have recently attempted to identify T-cell populations in the vaginal mucosa of naive and Candida-infected rats, in line with the previously mentioned differences in the T-cell population between mouse and rats [3). We found that in the rat vagina 60% of vaginal lymphocytes (VL) were CD3+ T-cells, while two-thirds of those expressed the

a1~ and one-third the -y18 T-cell receptor (TCR), with some slight fluctuations occurring during C. albicans infection. Importantly. however, we noticed remarkable changes in the CD4+/CD8+ T-cell ratio, during subsequent fungal infections, particularly for the cell bearing the CD25 (IL-2 receptor a) activation marker. In fact, an increased number of both CD4+ a113 TcR and CD4+/CD25 + VL was observed after the second and the third Candida challenge, reversing the high initial CD8+ cell number of control. estrogen-treated but uninfected rats. During a

third Candida challenge, VL showed proliferative activity, in a dose-dependent manner, with a mannoprotein fraction of C. albicans. These local T-cell modulations, which have no apparent counterparts in the local T-cell modulations in the mouse model, were not paralleled by similar changes at the systemic levels. However, these cells were fully responsive to polyclonal stimulants, demonstrating that in our model anti-Candida CMI at vaginal level was a true finding and was coupled with an alteration in T-cell vaginal repertoire (Fig. 5). This was also confirmed by the analysis of the cytokines secreted in the vaginal fluid of Candida-infected rats. In fact, high levels of IL-I2 during the first, immunizing infection, followed by progressively increasing amounts of 1L-2 and IFN-"( during the second and the third infections but not 1L-4 or IL-5 were found. Altogether, these results show that a Th-I-restricted response can be induced at the vaginal level by repeated, protective Candida vaginal challenge. What remains to be established in future studies is the relationship between CMI, Th-I elicitation, and protective Ab responses. In addition, our results open the way to addressing the question of adoptive transfer of vaginal T-cells.