Palacios R
Eur J Immunol. 1984 Jul;14(7):599-605. doi: 10.1002/eji.1830140704.
MRL/MP-lpr/lpr (MRL/lpr) mice develop a lupus-like autoimmune disease and a massive generalized lymphadenopathy associated with proliferation of nonmalignant Thy-1+ Lyt-1+ cells. The mechanism(s) leading to outgrowth of these cells is unknown. We report here that Thy-1+, Lyt-1+, Lyt2- lymphocytes from spleens of MRL/lpr mice, but not from several strains of normal mice, spontaneously secrete IL3. The presence of IL3 is shown by: (a) the ability of the supernatants from unstimulated spleen cells of MRL/lpr (MRL/lpr SUP) to support growth of IL3 but not IL2 addicted cells and (b) the growth-promoting activity in MRL/lpr SUP was absorbed with IL3-dependent cells but not with IL2-dependent cells. Spontaneous release of IL3 was detected in supernatants from spleen cells of 6-week-old MRL/lpr mice and the titers of IL3 activity increased with age. Nylon wool-enriched cells from spleens of MRL/lpr mice proliferated in response to purified IL3 and IL3 secreted by MRL/lpr T cells, in a manner similar to nylon wool-passed cells from normal mice. The cells responding to both sources of IL3 were Thy-1+, Lyt-1+, Lyt-2-. Thus, Thy-1+, Lyt-1+,2- cells from spleen of MRL/lpr mice spontaneously secrete IL3 and respond normally to this lymphokine. Four Thy-1+, Lyt-1+,2- cell lines derived from unstimulated spleen cells of MRL/lpr mice were established in culture with IL3. These IL3-sensitive T cell lines help syngeneic and H-2 compatible normal small "resting" B cells to mature into plasma cells secreting predominantly IgG1, IgG2 and IgA. Taken together, these data and previous findings that T cells from MRL/lpr mice have an impaired production of and response to IL2, strongly suggest that abnormal production of IL3 may account for the outgrowth of Thy-1+, Lyt-1+,2- cells in the MRL/lpr mouse. Finally, a mechanism linking abnormal production of IL3 and B cell hyperactivity in these animals is proposed.
MRL/MP-lpr/lpr（MRL/lpr）小鼠会患上类似狼疮的自身免疫性疾病以及与非恶性Thy-1⁺Lyt-1⁺细胞增殖相关的广泛性淋巴结病。导致这些细胞增生的机制尚不清楚。我们在此报告，来自MRL/lpr小鼠脾脏的Thy-1⁺、Lyt-1⁺、Lyt2⁻淋巴细胞（而非来自几种正常小鼠品系的淋巴细胞）会自发分泌IL3。IL3的存在通过以下方式得以证明：（a）MRL/lpr未刺激脾细胞的上清液（MRL/lpr SUP）支持IL3依赖细胞而非IL2依赖细胞生长的能力；（b）MRL/lpr SUP中的生长促进活性被IL3依赖细胞而非IL2依赖细胞吸收。在6周龄MRL/lpr小鼠脾细胞的上清液中检测到IL3的自发释放，且IL3活性滴度随年龄增加。来自MRL/lpr小鼠脾脏经尼龙毛富集的细胞对纯化的IL3以及MRL/lpr T细胞分泌的IL3有增殖反应，其方式类似于来自正常小鼠经尼龙毛处理的细胞。对两种IL3来源均有反应的细胞为Thy-1⁺、Lyt-1⁺、Lyt-2⁻。因此，来自MRL/lpr小鼠脾脏的Thy-1⁺、Lyt-1⁺、2⁻细胞会自发分泌IL3并对这种淋巴因子正常反应。用IL3在培养中建立了4个源自MRL/lpr小鼠未刺激脾细胞的Thy-1⁺、Lyt-1⁺、2⁻细胞系。这些对IL3敏感的T细胞系帮助同基因且H-2相容的正常小型“静止”B细胞成熟为主要分泌IgG1、IgG2和IgA的浆细胞。综上所述，这些数据以及之前关于MRL/lpr小鼠T细胞产生和对IL2反应受损的发现，强烈表明IL3的异常产生可能是MRL/lpr小鼠中Thy-1⁺、Lyt-1⁺、2⁻细胞增生的原因。最后，提出了一种将这些动物中IL3的异常产生与B细胞过度活跃联系起来的机制。
