Local anticandidal immune responses in a rat model of vaginal infection byand protection against Candida albicans

Humoral (antibody [Ab]) and cellular Candida-specific immune responses in t he vaginas of pseudoestrus rats were investigated during three successive i nfections by Candida albicans, After the first, protective infection, Abs a gainst mannan and aspartyl proteinase antigens were present in the vaginal fluid, and their titers clearly increased during the two subsequent, rapidl y healing infections, In all animals, about 65 and 10% of vaginal lymphocyt es (VL) were CD3+ (T cells) and CD3(-) CD5(+) (B cells), respectively. Two- thirds of the CD3(+) T cells expressed the alpha/beta and one-third express ed the gamma/delta T-cell receptor (TCR), This proportion slightly fluctuat ed during the three rounds of C. albicans infection, but no significant dif ferences between infected and noninfected rats were found. More relevant we re the changes in the CD CD4(+)/CD8(+) T-cell ratio, particularly for cells bearing the CD25 (interleukin-2 receptor alpha) marker. In fact, a progres sively increased number of both CD4(+) alpha/beta TCR and CD4(+) CD25(+) VL was observed after the second and third Candida challenges, reversing the high initial CD8(+) cell number of controls (estrogenized but uninfected ra ts). The CD3(-) CD5(+) cells also almost doubled from the first to the thir d infection. Analysis of the cytokines secreted in the vaginal fluid of Can dida-infected rats showed high levels of interleukin 12 (IL-12) during the first infection, followed by progressively increasing amounts of IL-2 and g amma interferon during the subsequent infections. No IL-3 or IL-5 was ever detected. During the third infection, VL with in vitro proliferative activi ty in response to an immunodominant mannoprotein antigen of C, albicans wer e present in the vaginal tissue. No response to this antigen by mitogen-res ponsive blood, lymph node, and spleen cells was found. In summary, the pres ence of protective Ab and T helper type 1 cytokines in the vaginal fluids, the in vitro proliferation of vaginal lymphocytes in response to Candida an tigenic stimulation, and the increased number of activated CD4(+) cells and some special B lymphocytes after C. albicans challenge constitute good evi dence for induction of locally expressed Candida-specific Ab and cellular r esponses which are potentially involved in anticandidal protection at the v aginal level.