Blackstock R, Casadevall A
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Immunology. 1997 Nov;92(3):334-9. doi: 10.1046/j.1365-2567.1997.00357.x.
A hallmark of infection with Cryptococcus neoformans is depression of the immune system characterized by poor inflammatory responses and loss of delayed-type hypersensitivity (DTH) and antibody responses. T-suppressor cell (Ts) responses, elicited by the capsular polysaccharide (GXM) of the organism, are known to develop during infection. This study was undertaken to develop a method to inhibit the anti-GXM Ts response and thereby study the influence of the Ts response on immune responsiveness and survival in cryptococcosis. Antigen-presenting cells (APC), elicited with complete Freund's adjuvant (CFA), were treated in vitro with GXM (GXM-APC). The GXM-APC were injected intravenously into normal mice. These mice were resistant to induction of anti-GXM Ts cells when soluble GXM was administered in tolerogenic doses or when animals were infected with C. neoformans. Inhibition of the anti-GXM Ts response was specific to GXM as levan-APC did not inhibit induction of anti-GXM Ts cells. Inhibition of the anti-GXM Ts response could not be attributed to increased clearance of GXM due to induction of anti-GXM antibodies or other mechanisms. Anti-cryptococcal DTH responses were lost in mice by the second week of infection. However, treatment with GXM-APC, but not levan-APC, allowed mice to maintain their DTH response. GXM-APC pretreatment enhanced survival of infected mice compared with mice pretreated with levan-APC. These results show that GXM-APC induces immune responses that inhibit the induction of Ts responses and enhances DTH responses in infected mice. These responses correlate with enhanced survival after cryptococcal infection.
新型隐球菌感染的一个标志是免疫系统受到抑制，其特征为炎症反应不佳、迟发型超敏反应（DTH）丧失以及抗体反应缺失。已知机体的荚膜多糖（GXM）可引发T抑制细胞（Ts）反应，且该反应在感染过程中会逐渐形成。本研究旨在开发一种抑制抗GXM Ts反应的方法，从而研究Ts反应对隐球菌病免疫反应性和生存的影响。用完全弗氏佐剂（CFA）激发的抗原呈递细胞（APC），在体外与GXM共同处理（GXM - APC）。将GXM - APC静脉注射到正常小鼠体内。当以耐受剂量给予可溶性GXM或动物感染新型隐球菌时，这些小鼠对诱导抗GXM Ts细胞具有抗性。抗GXM Ts反应的抑制对GXM具有特异性，因为左聚糖 - APC不会抑制抗GXM Ts细胞的诱导。抗GXM Ts反应的抑制不能归因于由于诱导抗GXM抗体或其他机制导致的GXM清除增加。感染后第二周，小鼠的抗隐球菌DTH反应消失。然而，用GXM - APC处理而非左聚糖 - APC处理，可使小鼠维持其DTH反应。与用左聚糖 - APC预处理的小鼠相比，GXM - APC预处理可提高感染小鼠的存活率。这些结果表明，GXM - APC可诱导免疫反应，抑制Ts反应的诱导，并增强感染小鼠的DTH反应。这些反应与隐球菌感染后存活率的提高相关。
