Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2.
Analysis of T cell function in autoimmune murine strains. Defects in production and responsiveness to interleukin 2.
复制标题
自身免疫性鼠菌株中T细胞功能的分析。生产缺陷和对白介素2的反应性。
DOI：
10.1084/jem.154.3.791
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发表时间：
1981-09-01
影响因子：
15.3
通讯作者：
Dixon, F J
中科院分区：
文献类型：
--
作者：
Altman, A;Theofilopoulos, A N;Weiner, R;Katz, D H;Dixon, F J
在本文报道的研究中，我们分析了表现出系统性红斑狼疮（SLE）样综合征的小鼠菌株[MRL， BXSB， NZB和（NZB x NZWF1）]中T细胞生长因子（最近称为白细胞介素2 (IL-2)）的产生和消耗，以及一些细胞介导的免疫功能。研究了幼年（4-6周）或老年（4-8个月）自身免疫性小鼠或正常小鼠在体外用豆豆蛋白A （Con A）刺激后的以下T细胞功能：(b)培养上代细胞中IL-2水平；(c)对IL-2的反应和吸附能力。此外，我们还分析了这些菌株在同种异体混合白细胞培养中的增殖活性和同种异体细胞毒性T淋巴细胞前体（CTLp）的频率。Con - a诱导的有丝分裂反应和IL-2的产生在3-6周龄时出现，在早期，严重的SLE发展株MRL- mp -lpr/lpr （MRL/l）和雄性BXSB中，并在此后发展。类似的缺陷出现在MRL/Mp-+/+和（NZB x NZW）F1杂交小鼠的较晚阶段，它们发展为晚期疾病。对老年MRL/l小鼠肿大淋巴结和脾脏细胞的详细分析表明，这些细胞：(a)即使在外源性IL-2存在的情况下，对Con a或异体刺激细胞的反应也很差；(b)不抑制正常脾细胞产生IL-2；(c)相对不能吸附或灭活IL-2；(d)肠系膜淋巴结抗h -2b CTLp频率明显降低，脾脏正常。这些结果表明，MRL/l小鼠中增殖的Thy-1.2+、Lyt-1+ T细胞对有丝分裂刺激的反应、IL-2的产生和IL-2受体位点的表达存在缺陷。这些缺陷与MRL/l疾病的相关性以及IL-2在自身免疫中的作用仍有待确定。
In the studies reported here, we have analyzed the production and consumption of T cell growth factor, more recently termed interleukin 2 (IL-2), as well as some cell-mediated immune functions, in murine strains [MRL, BXSB, NZB, and (NZB x NZWF1] manifesting systemic lupus erythematosus (SLE)-like syndromes. Young (4-6 wk) or old (4-8 mo) autoimmune or normal mice were studied and compared with regard to the following T cell functions in vitro after stimulation with concanavalin A (Con A): (a) mitogenic response; (b) IL-2 levels in culture supernates; and (c) the ability to respond to and adsorb IL-2. In addition, proliferative activity in the allogeneic mixed leukocyte culture and frequency of alloreactive cytotoxic T lymphocyte precursors (CTLp) were analyzed in some of these strains. Reduced Con A-induced mitogenic responses and IL-2 production appeared at 3-6 wk of age in the early, severe SLE developing strains MRL-Mp-lpr/lpr (MRL/l) and male BXSB and progressed thereafter. Similar defects appeared at a later stage in MRL/Mp-+/+ and (NZB x NZW)F1 hybrid mice, which develop late disease. Detailed analysis of cells from the enlarged lymph nodes and spleens of older MRL/l mice demonstrated that such cells: (a) responded poorly to Con A or allogeneic stimulator cells, even in the presence of exogenous IL-2; (b) did not suppress IL-2 production by normal spleen cells; (c) were relatively incapable of adsorbing or inactivating IL-2; and (d) had a markedly reduced anti-H-2b CTLp frequency in the mesenteric lymph nodes but a normal one in spleen. These results indicate that the proliferating Thy-1.2+, Lyt-1+ T cells in MRL/l mice are defective in their responses to mitogenic stimuli, in IL-2 production, and in expression of acceptor sites for IL-2. The relevance of these defects to the MRL/l disease as well as to the role of IL-2 in autoimmunity in general remains to be determined.