Kook A I, Trainin N
J Exp Med. 1974 Jan 1;139(1):193-207. doi: 10.1084/jem.139.1.193.
Experiments reported here were performed to understand the mechanism by which THF increases the immunocompetence of spleen cells from NTx mice. Dibutyryl cAMP or substances which increase intracellular levels of cAMP in lymphocytes such as Poly(A:U), theophylline, or PGE(2) were shown to mimic the effect of THF and confer reactivity in an in vitro GvH response to spleen cells from NTx mice. Flufenamic acid, an antagonist to PGE(2), was shown to inhibit the induction of competence by this substance. It was found that THF induces competence by activating membranal adenyl cyclase which leads to a rise in intracellular cAMP in thymus-derived cells only. These biochemical changes occur before antigenic stimulation and are unrelated to antigenic challenge. These findings indicate that THF exerts its effect via cAMP and are in agreement with the concepts which permit to classify THF as a thymus hormone.
本文所报道的实验旨在了解四氢叶酸(THF)提高去胸腺(NTx)小鼠脾细胞免疫活性的机制。已证实,二丁酰环磷腺苷(Dibutyryl cAMP)或能提高淋巴细胞内cAMP水平的物质,如聚腺苷酸:尿苷酸(Poly(A:U))、茶碱或前列腺素E2(PGE(2)),可模拟THF的作用,并赋予NTx小鼠脾细胞在体外移植物抗宿主(GvH)反应中的反应性。已证实,氟芬那酸(一种PGE(2)拮抗剂)可抑制该物质诱导的免疫活性。研究发现,THF通过激活膜腺苷酸环化酶来诱导免疫活性,这仅导致胸腺来源细胞内的cAMP升高。这些生化变化发生在抗原刺激之前,且与抗原攻击无关。这些发现表明,THF通过cAMP发挥作用,这与将THF归类为胸腺激素的概念相符。