de Bernardis F, Santoni G, Boccanera M, Spreghini E, Adriani D, Morelli L, Cassone A
Department of Bacteriology and Medical Mycology, University of Camerino, Camerino, Italy.
Infect Immun. 2000 Jun;68(6):3297-304. doi: 10.1128/IAI.68.6.3297-3304.2000.
Humoral (antibody [Ab]) and cellular Candida-specific immune responses in the vaginas of pseudoestrus rats were investigated during three successive infections by Candida albicans. After the first, protective infection, Abs against mannan and aspartyl proteinase antigens were present in the vaginal fluid, and their titers clearly increased during the two subsequent, rapidly healing infections. In all animals, about 65 and 10% of vaginal lymphocytes (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 expressed the gamma/delta T-cell receptor (TCR). This proportion slightly fluctuated during the three rounds of C. albicans infection, but no significant differences between infected and noninfected rats were found. More relevant were the changes in the CD4(+)/CD8(+) T-cell ratio, particularly for cells bearing the CD25 (interleukin-2 receptor alpha) marker. In fact, a progressively 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 rats). The CD3(-) CD5(+) cells also almost doubled from the first to the third infection. Analysis of the cytokines secreted in the vaginal fluid of Candida-infected rats showed high levels of interleukin 12 (IL-12) during the first infection, followed by progressively increasing amounts of IL-2 and gamma interferon during the subsequent infections. No IL-4 or IL-5 was ever detected. During the third infection, VL with in vitro proliferative activity in response to an immunodominant mannoprotein antigen of C. albicans were present in the vaginal tissue. No response to this antigen by mitogen-responsive blood, lymph node, and spleen cells was found. In summary, the presence of protective Ab and T helper type 1 cytokines in the vaginal fluids, the in vitro proliferation of vaginal lymphocytes in response to Candida antigenic stimulation, and the increased number of activated CD4(+) cells and some special B lymphocytes after C. albicans challenge constitute good evidence for induction of locally expressed Candida-specific Ab and cellular responses which are potentially involved in anticandidal protection at the vaginal level.
在连续三次白色念珠菌感染期间，对假动情期大鼠阴道中的体液（抗体[Ab]）和细胞念珠菌特异性免疫反应进行了研究。在第一次保护性感染后，阴道液中存在抗甘露聚糖和天冬氨酸蛋白酶抗原的抗体，并且在随后两次迅速愈合的感染期间，它们的滴度明显升高。在所有动物中，阴道淋巴细胞（VL）中分别约65%和10%为CD3(+)（T细胞）和CD3(-) CD5(+)（B细胞）。三分之二的CD3(+) T细胞表达α/β，三分之一表达γ/δ T细胞受体（TCR）。在三轮白色念珠菌感染期间，这一比例略有波动，但未发现感染大鼠与未感染大鼠之间存在显著差异。更相关的是CD4(+)/CD8(+) T细胞比例的变化，特别是对于带有CD25（白细胞介素-2受体α）标记的细胞。事实上，在第二次和第三次念珠菌攻击后，观察到CD4(+)α/β TCR和CD4(+) CD25(+) VL的数量逐渐增加，扭转了对照组（雌激素化但未感染的大鼠）最初较高的CD8(+)细胞数量。从第一次感染到第三次感染，CD3(-) CD5(+)细胞数量也几乎增加了一倍。对念珠菌感染大鼠阴道液中分泌的细胞因子分析显示，在第一次感染期间白细胞介素12（IL-12）水平较高，随后在随后的感染期间IL-2和γ干扰素的量逐渐增加。从未检测到IL-4或IL-5。在第三次感染期间，阴道组织中存在对白色念珠菌的一种免疫显性甘露糖蛋白抗原具有体外增殖活性的VL。未发现丝裂原反应性血液、淋巴结和脾细胞对该抗原有反应。总之，阴道液中存在保护性抗体和1型辅助性T细胞细胞因子，阴道淋巴细胞在念珠菌抗原刺激下的体外增殖，以及白色念珠菌攻击后活化的CD4(+)细胞和一些特殊B淋巴细胞数量的增加，构成了诱导局部表达的念珠菌特异性抗体和细胞反应的有力证据，这些反应可能参与阴道水平的抗念珠菌保护。
