Murphy J W
University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Infect Immun. 1993 Nov;61(11):4750-9. doi: 10.1128/iai.61.11.4750-4759.1993.
Previous studies with a murine model have shown that immunization with cryptococcal culture filtrate antigen (CneF) emulsified in complete Freund adjuvant (CFA) induces two populations of anticryptococcal reactive CD4+ T cells. One population (TDH cells) transfers anticryptococcal delayed-type hypersensitivity (DTH), and the other population (Tamp cells) amplifies the anticryptococcal DTH response of given to recipient mice at the time of immunization of the recipient. Treatment of mice with cyclosporin A (CsA) ablates the induction of Tamp cells but not TDH cells. The present study focused on assessing the cytokines produced by spleen cells taken from CsA-treated and control (solvent-treated) mice at days 1, 2, 4, and 6 after immunization. Supernatants from the spleen cells cultured in vitro for 24 or 48 h in medium alone or with CneF, concanavalin A, or phorbol 12-myristate 13-acetate plus calcium ionophore were assessed for the presence of interleukin-2 (IL-2), gamma interferon (IFN-gamma), IL-4, IL-5, and tumor necrosis factor. Spleen cells from CneF-CFA-treated mice produced IL-2 and IFN-gamma, but not IL-4 or IL-5, constitutively and in response to CneF, indicating that CneF-CFA induces a Th1 response. Tumor necrosis factor was not produced. Anticryptococcal TDH cells developed in spleens in which there were low levels of IFN-gamma and IL-2 (CsA-treated, immunized mice), whereas anticryptococcal Tamp cells along with TDH cells matured in spleens in which production of IFN-gamma and IL-2 was high (solvent-treated, immunized mice). The data also suggest that IL-2 and IFN-gamma produced by Tamp cells early after adoptive transfer are influential in the development of the amplified anticryptococcal DTH response that has been observed in Tamp cell-recipient mice.
先前对小鼠模型的研究表明，用完全弗氏佐剂（CFA）乳化的新型隐球菌培养滤液抗原（CneF）进行免疫可诱导出两类抗新型隐球菌反应性CD4+T细胞。一类细胞（TDH细胞）可传递抗新型隐球菌迟发型超敏反应（DTH），另一类细胞（Tamp细胞）可增强在受体小鼠免疫时给予受体的抗新型隐球菌DTH反应。用环孢素A（CsA）处理小鼠可消除Tamp细胞的诱导，但不影响TDH细胞。本研究的重点是评估免疫后第1、2、4和6天从经CsA处理的小鼠和对照（溶剂处理）小鼠脾脏中获取的细胞所产生的细胞因子。将脾脏细胞在单独培养基中或与CneF、伴刀豆球蛋白A或佛波醇12-肉豆蔻酸酯13-乙酸酯加钙离子载体一起体外培养24或48小时后，检测上清液中白细胞介素-2（IL-2）、γ干扰素（IFN-γ）、IL-4、IL-5和肿瘤坏死因子的存在情况。经CneF-CFA处理的小鼠脾脏细胞组成性地并在对CneF反应时产生IL-2和IFN-γ，但不产生IL-4或IL-5，这表明CneF-CFA诱导了Th1反应。未产生肿瘤坏死因子。抗新型隐球菌TDH细胞在IFN-γ和IL-2水平较低的脾脏中发育（经CsA处理的免疫小鼠），而抗新型隐球菌Tamp细胞以及TDH细胞在IFN-γ和IL-2产生较高的脾脏中成熟（经溶剂处理的免疫小鼠）。数据还表明，过继转移后早期Tamp细胞产生的IL-2和IFN-γ对在Tamp细胞受体小鼠中观察到的增强的抗新型隐球菌DTH反应的发展有影响。
