Zlotnik A, Godfrey D I, Fischer M, Suda T
DNAX Research Institute, Palo Alto, CA 94304.
J Immunol. 1992 Aug 15;149(4):1211-5.
This study follows our previous investigation describing the production of four cytokines (IL-2, IL-4, IFN-gamma, and TNF-alpha) by subsets of thymocytes defined by the expression of CD3, 4, 8, and 25. Here we investigate in greater detail subpopulations of CD4-CD8- double negative (DN) thymocytes. First we divided immature CD25-CD4-CD8-CD3- (CD25- triple negative) (TN) thymocytes into CD44+ and CD44- subsets. The CD44+ population includes very immature precursor T cells and produced high titers of IL-2, TNF-alpha, and IFN-gamma upon activation with calcium ionophore and phorbol ester. In contrast, the CD44- subset of CD25- TN thymocytes did not produce any of the cytokines studied under similar activation conditions. This observation indicates that the latter subset, which differentiates spontaneously in vitro into CD4+CD8+, already resembles CD4+CD8+ thymocytes (which do not produce any of the tested cytokines). We also subdivided the more mature CD3+ DN thymocytes into TCR-alpha beta- and TCR-gamma delta-bearing subsets. These cells produced cytokines upon activation with solid phase anti-CD3 mAb. gamma delta TCR+ DN thymocytes produced IL-2, IFN-gamma and TNF-alpha, whereas alpha beta TCR+ DN thymocytes produced IL-4, IFN-gamma, and TNF-alpha but not IL-2. We then studied alpha beta TCR+ DN T cells isolated from the spleen and found a similar cytokine production profile. Furthermore, splenic alpha beta TCR+ DN cells showed a TCR V beta gene expression profile reminiscent of alpha beta TCR+ DN thymocytes (predominant use of V beta 8.2). These observations suggest that at least some alpha beta TCR+ DN splenocytes are derived from alpha beta TCR+ DN thymocytes and also raises the possibility that these cells may play a role in the development of Th2 responses through their production of IL-4.
本研究延续了我们之前的调查，该调查描述了由CD3、4、8和25的表达所定义的胸腺细胞亚群产生四种细胞因子（IL-2、IL-4、IFN-γ和TNF-α）的情况。在此，我们更详细地研究CD4-CD8-双阴性（DN）胸腺细胞的亚群。首先，我们将未成熟的CD25-CD4-CD8-CD3-（CD25-三阴性）（TN）胸腺细胞分为CD44+和CD44-亚群。CD44+群体包括非常未成熟的前体T细胞，在用钙离子载体和佛波酯激活后产生高滴度的IL-2、TNF-α和IFN-γ。相比之下，CD25-TN胸腺细胞的CD44-亚群在类似的激活条件下不产生所研究的任何细胞因子。这一观察结果表明，后一个亚群在体外自发分化为CD4+CD8+，已经类似于CD4+CD8+胸腺细胞（不产生任何测试细胞因子）。我们还将更成熟的CD3+DN胸腺细胞细分为携带TCR-αβ和TCR-γδ的亚群。这些细胞在用固相抗CD3单克隆抗体激活后产生细胞因子。γδTCR+DN胸腺细胞产生IL-2、IFN-γ和TNF-α，而αβTCR+DN胸腺细胞产生IL-4、IFN-γ和TNF-α，但不产生IL-2。然后，我们研究了从脾脏中分离的αβTCR+DN T细胞，发现了类似的细胞因子产生谱。此外，脾脏αβTCR+DN细胞显示出TCR Vβ基因表达谱，让人联想到αβTCR+DN胸腺细胞（主要使用Vβ8.2）。这些观察结果表明，至少一些αβTCR+DN脾细胞来源于αβTCR+DN胸腺细胞，也增加了这些细胞可能通过产生IL-4在Th2反应发展中发挥作用的可能性。
