Patterns of Expression of Vaginal T-Cell Activation Markers during Estrogen-Maintained Vaginal Candidiasis

Abstract

: The immunosuppressive activity of estrogen was further investigated by assessing the pattern of expression of CD25, CD28, CD69, and CD152 on vaginal T cells during estrogen-maintained vaginal candidiasis. A precipitous and significant decrease in vaginal fungal burden toward the end of week 3 postinfection was concurrent with a significant increase in vaginal lymphocyte numbers. During this period, the percentage of CD3+, CD3+CD4+, CD152+, and CD28+ vaginal T cells gradually and significantly increased. The percentage of CD3+ and CD3+CD4+ cells increased from 43% and 15% at day 0 to 77% and 40% at day 28 postinfection. Compared with 29% CD152+ vaginal T cells in naive mice, > 70% of vaginal T cells were CD152+ at day 28 postinfection. In conclusion, estrogen-maintained vaginal candidiasis results in postinfection time-dependent changes in the pattern of expression of CD152, CD28, and other T-cell markers, suggesting that T cells are subject to mixed suppression and activation signals.

Figure 1

Vaginal and splenic fungal burdens were evaluated in phosphate-buffered saline-treated control mice, estrogen-treated Candida albicans-infected experimental mice, and untreated C. albicans-infected control mice at days 7, 14, 21, 28, and 35 postinfection. The data shown represent mean CFU/tissue ± SD as calculated from three separate experiments using five to six mice/time point/experiment.

Figure 2

Absolute numbers of vaginal (A) and splenic (B) lymphocytes isolated from phosphate-buffered saline-treated control mice and estrogen-treated Candida albicans-infected experimental mice at days 7, 14, 21, 28, and 35 postinfection. Cell counts were plotted against the time points at which cells were harvested. The mean number of lymphocytes/tissue ± SEM was calculated based on data from three separate experiments, five to six mice/time point/experiment.

Figure 3

Vaginal lymphocytes isolated from phosphate-buffered saline-treated control mice and from estrogen-treated Candida albicans-infected experimental mice at day 28 postinfection were separately pooled from five to six mice and stained with anti-CD3 and anti-CD4 for two-colour flow cytometric (FCM) analysis or with anti-CD28, or anti-CD69 or anti-CD152 for single-colour FCM analysis. The data shown are representative of three separate experiments

Figure 4

Summary of the mean percentage expression ± SD of CD25, CD28, CD69, and CD152 on (A) vaginal and (B) splenic T cells isolated from estrogen-treated Candida albicans-infected experimental mice at days 0, 7, 14, 21, 28, and 35 postinfection. Means ± SD were calculated based on three separate experiments; at each time point, tissue lymphocytes were isolated from five to six mice and pooled prior to staining and flow cytometric analysis.