Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.
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DOI：
10.1084/jem.169.1.59
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发表时间：
1989-01-01
期刊：
影响因子：
--
通讯作者：
Locksley RM
中科院分区：
文献类型：
--
作者：
Heinzel FP;Sadick MD;Holaday BJ;Coffman RL;Locksley RM
我们在基因易感的BALB/c小鼠和抗性的C57BL/6小鼠感染利什曼原虫主要株后的特定时间，从脾脏和淋巴结中纯化多聚腺苷酸（poly(A)+）mRNA。使用Northern杂交测定白细胞介素 - 2（IL - 2）、干扰素 - γ（IFN - γ）、白细胞介素 - 4（IL - 4）和白细胞介素 - 1β（IL - 1β）mRNA的稳态水平。感染后，BALB/c和C57BL/6小鼠感染器官中的IL - 2 mRNA水平相当，但IFN - γ和IL - 4 mRNA水平呈相反表达。除感染4周和6周时脾脏的IFN - γ mRNA水平短暂相当外，C57BL/6引流淋巴结和脾脏中的IFN - γ mRNA水平显著高于BALB/c小鼠。相反，IL - 4 mRNA仅在BALB/c小鼠的淋巴结和脾脏中明显，而在C57BL/6小鼠中不明显。BALB/c小鼠中IL - 1β mRNA的组织水平高10 - 20倍。BALB/c小鼠用GK1.5单克隆抗体预处理，这种操作通过暂时耗竭L3T4⁺细胞促进后续感染的愈合。感染8周时，此时淋巴器官已重新被L3T4⁺细胞填充，经GK1.5预处理的BALB/c小鼠产生IFN - γ，但不产生IL - 4信息。感染的BALB/c小鼠血清IgE水平显著升高，但感染的C57BL/6小鼠或经GK1.5预处理的BALB/c小鼠中不升高，这与非愈合小鼠中IL - 4的体内生物学活性一致。用中和性抗IL - 4抗体治疗感染的BALB/c小鼠可消除血清IgE的升高，并根据病变大小和溃疡情况以及组织寄生虫数量的减少来评估，显著减缓疾病进展。先前已表明对利什曼原虫感染的保护性和有害反应均依赖于L3T4⁺细胞。我们的研究结果与愈合小鼠中产生保护性IFN - γ的Th1细胞的差异扩增以及非愈合小鼠中产生有害IL - 4的Th2细胞的扩增一致。利什曼病期间IFN - γ和IL - 4基因表达的反比关系可能是利什曼原虫以及可能其他细胞内寄生虫慢性感染期间细胞免疫和体液免疫发生分歧的基础。
We purified poly(A)+ mRNA from the spleen and lymph nodes at designated times after infection with Leishmania major in genetically susceptible BALB/c and resistant C57BL/6 mice. The steady-state levels of IL-2, IFN- gamma, IL-4, and IL-1 beta mRNA were determined using Northern hybridizations. IL-2 mRNA levels in the infected organs of BALB/c and C57BL/6 mice were comparable after infection, but IFN-gamma and IL-4 mRNA levels were reciprocally expressed. Levels of IFN-gamma mRNA in C57BL/6 draining nodes and spleen were significantly greater than in BALB/c mice except at 4 and 6 wk of infection, when splenic IFN-gamma mRNA levels were transiently comparable. In contrast, IL-4 mRNA was apparent only in BALB/c and not in C57BL/6 nodes and spleen. Tissue levels of IL-1 beta mRNA were 10-20-fold greater in BALB/c mice. BALB/c mice were pretreated with GK1.5 mAb, a manipulation that promotes healing of subsequent infection by transiently depleting L3T4+ cells. At 8 wk of infection, by which time lymphoid organs were repopulated with L3T4+ cells, GK1.5-pretreated BALB/c mice produced IFN-gamma, but not IL-4 message. Serum levels of IgE were markedly elevated in infected BALB/c, but not in infected C57BL/6 or GK1.5-pretreated BALB/c mice, consistent with in vivo biologic activity of IL-4 in nonhealing mice. Treatment of infected BALB/c mice with neutralizing anti-IL-4 antibody abolished the elevation of serum IgE and significantly attenuated the progression of disease as assessed by size and ulceration of the lesion, and by reduction in the number of tissue parasites. Both protective and deleterious responses to Leishmania infection have previously been shown to be L3T4+ cell dependent. Our findings are consistent with the differential expansion of protective, IFN-gamma-producing Th1 cells in healing mice, and the expansion of deleterious, IL-4-producing Th2 cells in nonhealing mice. The inverse relationship of IFN-gamma and IL-4 gene expression during leishmaniasis may underlie the divergence of cellular and humoral immunity that occurs during chronic infection with Leishmania and possibly other intracellular parasites.
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影响因子：
3.1
作者：
KIRKPATRICK, CE;FARRELL, JP
通讯作者：
FARRELL, JP
DOI：
10.1073/pnas.83.7.2061
发表时间：
1986-04-01
影响因子：
11.1
作者：
LEE, F;YOKOTA, T;ARAI, K
通讯作者：
ARAI, K
影响因子：
2.1
作者：
HEINZEL, FP;SADICK, MD;LOCKSLEY, RM
通讯作者：
LOCKSLEY, RM
影响因子：
15.3
作者：
Howard, J G;Hale, C;Liew, F Y
通讯作者：
Liew, F Y
DOI：
10.1084/jem.162.1.324
发表时间：
1985-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blackwell JM;Ezekowitz RA;Roberts MB;Channon JY;Sim RB;Gordon S
通讯作者：
Gordon S