Fischer M, MacNeil I, Suda T, Cupp J E, Shortman K, Zlotnik A
Department of Immunology, DNAX Research Institute, Palo Alto, CA 94304.
J Immunol. 1991 May 15;146(10):3452-6.
We have studied the ability of subpopulations of activated thymocytes to produce four cytokines (IL-2, IL-4, IFN-gamma and TNF-alpha) which are believed to play roles in T cell development. Supernatants from various thymocyte subsets activated with calcium ionophore and PMA were tested for these cytokines. All CD3hi thymocyte subsets (CD4+8-, CD4-8- and CD4-8+) produced high titers of these four cytokines except CD3+4-8+ thymocytes, which did not produce IL-4. In contrast, CD4+8+ thymocytes did not produce any detectable cytokines. CD3-4-8- thymocytes produced IL-2, IFN-gamma, and TNF-alpha (but not IL-4) when activated by calcium ionophore + PMA and IL-1. We then separated CD3-4-8- thymocytes into IL-2R+ and IL-2R-. CD3-4-8-IL-2R+ thymocytes only produced small amounts of IL-2 when activated with calcium ionophore + PMA + IL-1, whereas CD3-4-8-IL-2R- thymocytes did not require IL-1 to produce IL-2, IFN-gamma, and TNF-alpha. Finally, CD4-8+3- thymocytes (an immature population believed to be an intermediate between CD3-4-8- and CD4+8+ thymocytes) only produced marginally detectable levels of IL-2 upon stimulation with calcium ionophore, PMA, and the addition of IL-1 did not result in increased levels of cytokine production. These observations indicate discrete patterns of cytokine production by the subsets studied and suggest specific controls of cytokine gene expression during T cell development.
我们研究了活化胸腺细胞亚群产生四种细胞因子（白细胞介素-2、白细胞介素-4、γ干扰素和肿瘤坏死因子-α）的能力，这些细胞因子被认为在T细胞发育中发挥作用。用钙离子载体和佛波酯激活的各种胸腺细胞亚群的培养上清液进行了这些细胞因子的检测。除了不产生白细胞介素-4的CD3⁺4⁻8⁺胸腺细胞外，所有CD3高表达的胸腺细胞亚群（CD4⁺8⁻、CD4⁻8⁻和CD4⁻8⁺）都产生高滴度的这四种细胞因子。相比之下，CD4⁺8⁺胸腺细胞不产生任何可检测到的细胞因子。CD3⁻4⁻8⁻胸腺细胞在被钙离子载体+佛波酯和白细胞介素-1激活时产生白细胞介素-2、γ干扰素和肿瘤坏死因子-α（但不产生白细胞介素-4）。然后我们将CD3⁻4⁻8⁻胸腺细胞分为白细胞介素-2受体阳性和白细胞介素-2受体阴性亚群。CD3⁻4⁻8⁻白细胞介素-2受体阳性胸腺细胞在用钙离子载体+佛波酯+白细胞介素-1激活时仅产生少量白细胞介素-2，而CD3⁻4⁻8⁻白细胞介素-2受体阴性胸腺细胞产生白细胞介素-2、γ干扰素和肿瘤坏死因子-α则不需要白细胞介素-1。最后，CD4⁻8⁺3⁻胸腺细胞（一种被认为是CD3⁻4⁻8⁻和CD4⁺8⁺胸腺细胞之间中间体的未成熟群体）在用钙离子载体刺激时仅产生微量可检测水平的白细胞介素-2，添加白细胞介素-1并不会导致细胞因子产生水平增加。这些观察结果表明所研究的亚群具有不同的细胞因子产生模式，并提示在T细胞发育过程中细胞因子基因表达存在特定调控。
