Ferens W A, Goff W L, Davis W C, Fox L K, Deobald C, Hamilton M J, Bohach G A
Department of Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow 83844, USA.
J Nat Toxins. 1998 Oct;7(3):193-213.
Persistent intramammary infections of dairy cows with Staphylococcus aureus may involve immunosuppression mediated by bacterial toxins such as enterotoxins and other super-antigens (SAgs). Previously we found that stimulation of bovine PBMC with staphylococcal enterotoxin C (SEC) induced a unique phenotype of activated CD8+ T cells expressing a newly identified activation molecule, ACT3. In the present study we found that SEC induced the expression of interleukin (IL)-4 and IL-10 mRNAs, two cytokines associated with type 2 responses. Elevated levels of IL-4 and IL-10, observed between day 0 and day 4 of culture, were associated with temporary inhibition of proliferative responses of T cells, evidenced by a decrease in numbers of CD4+ T cells and a small increase in numbers of CD8+ T cells. Vigorous proliferation of T cells occurred between days 4 and 7 of culture and with a bias towards CD8+ T cells. Acquisition of the ACT3+ phenotype by CD8+ T cells was preceded by induction of IL-4 mRNA. Thus, in the bovine system, SAgs may hinder protective responses by inducing type 2 cytokines, which interfere with immune clearance of many microbial pathogens. The results of the study are consistent with the hypothesis that SAgs are involved in immunosuppression, and suggest possible immunomodulatory mechanisms.
金黄色葡萄球菌引起的奶牛持续性乳腺内感染可能涉及由细菌毒素如肠毒素和其他超抗原（SAgs）介导的免疫抑制。此前我们发现，用葡萄球菌肠毒素C（SEC）刺激牛外周血单核细胞（PBMC）可诱导表达新鉴定的激活分子ACT3的活化CD8⁺ T细胞呈现独特表型。在本研究中，我们发现SEC诱导了白细胞介素（IL）-4和IL-10 mRNA的表达，这两种细胞因子与2型反应相关。在培养的第0天至第4天观察到的IL-4和IL-10水平升高与T细胞增殖反应的暂时抑制有关，这表现为CD4⁺ T细胞数量减少和CD8⁺ T细胞数量略有增加。T细胞在培养的第4天至第7天发生旺盛增殖，且偏向于CD8⁺ T细胞。CD8⁺ T细胞获得ACT3⁺表型之前先诱导了IL-4 mRNA的表达。因此，在牛的系统中，SAgs可能通过诱导2型细胞因子来阻碍保护性反应，这些细胞因子会干扰许多微生物病原体的免疫清除。该研究结果与SAgs参与免疫抑制的假说一致，并提示了可能的免疫调节机制。
