Pearce E J, Caspar P, Grzych J M, Lewis F A, Sher A
Immunology and Cell Biology Section, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
J Exp Med. 1991 Jan 1;173(1):159-66. doi: 10.1084/jem.173.1.159.
In the mouse, infection with Schistosoma mansoni results in an egg-producing infection and associated disease, whereas vaccination with attenuated larval stages produces a substantial and specific immunity in the absence of egg-induced pathology. Preliminary data showing enhanced interleukin-5 (IL-5) production by T cells from infected mice and interferon gamma (IFN-gamma) synthesis by cells from vaccinated animals (7), suggested differential CD4+ subset stimulation by the different parasite stimuli. To confirm this hypothesis, lymphocytes from vaccinated or infected animals were compared for their ability to produce IFN-gamma and IL-2 (secreted by Th1 cells) as compared with IL-4 and IL-5 (characteristic Th2 cytokines). After stimulation with specific antigen or mitogen, T cells from vaccinated mice or prepatently infected animals responded primarily with Th1 lymphokines, whereas lymphocytes from patently infected mice instead produced Th2 cytokines. The Th2 response in infected animals was shown to be induced by schistosome eggs and directed largely against egg antigens, whereas the Th1 reactivity in vaccinated mice was triggered primarily by larval antigens. Interestingly, Th1 responses in mice carrying egg-producing infections were found to be profoundly downregulated. Moreover, the injection of eggs into vaccinated mice resulted in a reduction of antigen and mitogen-stimulated Th1 function accompanied by a coincident expression of Th2 responses. Together, the data suggest that coincident with the induction of Th2 responses, murine schistosome infection results in an inhibition of potentially protective Th1 function. This previously unrecognized downregulation of Th1 cytokine production may be an important immunological consequence of helminth infection related to host adaptation.
在小鼠中，感染曼氏血吸虫会导致产生虫卵的感染及相关疾病，而用减毒幼虫阶段进行疫苗接种则会在无虫卵诱导病理的情况下产生显著且特异的免疫力。初步数据显示，感染小鼠的T细胞产生白细胞介素-5（IL-5）增多，而接种疫苗动物的细胞合成干扰素γ（IFN-γ）（7），这表明不同的寄生虫刺激对CD4 +亚群有不同的刺激作用。为了证实这一假设，将接种疫苗或感染动物的淋巴细胞在产生IFN-γ和IL-2（由Th1细胞分泌）的能力方面与IL-4和IL-5（典型的Th2细胞因子）进行比较。用特异性抗原或丝裂原刺激后，接种疫苗小鼠或处于潜伏期感染动物的T细胞主要产生Th1淋巴细胞因子，而处于明显感染状态小鼠的淋巴细胞则产生Th2细胞因子。结果表明，感染动物中的Th2反应是由血吸虫卵诱导的，并且主要针对虫卵抗原，而接种疫苗小鼠中的Th1反应主要由幼虫抗原触发。有趣的是，发现携带产生虫卵感染的小鼠中的Th1反应被显著下调。此外，向接种疫苗的小鼠注射虫卵会导致抗原和丝裂原刺激的Th1功能降低，同时伴随Th2反应的表达。总之，数据表明，与Th2反应的诱导同时发生的是，小鼠血吸虫感染会导致潜在的保护性Th1功能受到抑制。这种先前未被认识到的Th1细胞因子产生的下调可能是与宿主适应性相关的蠕虫感染的重要免疫后果。
