Shin H C, Benbernou N, Esnault S, Guenounou M
Laboratoire d'Immunologie, Faculté de Pharmacie de Reims, France.
Cytokine. 1999 Apr;11(4):257-66. doi: 10.1006/cyto.1998.0433.
In the present study, the authors compared the interleukin 17 (IL-17 expression of human naive and phenotypically defined memory T cells as well as its regulation by cAMP pathway. Our data showed that IL-17 mRNA was highly expressed in memory human peripheral CD8(+)45RO+T cells and CD4(+)45RO+T cells when peripheral blood mononuclear cells were first stimulated with ionomycin/PMA. IL-17 expression in memory CD8(+)T cells required accessory signals since culture of ionomycin/PMA-activated CD8(+)45RO+T cells alone did not result to IL-17 expression. In contrast, memory CD4(+)T cell population seems to be more independent. IL-17 and interferon gamma(IFN-gamma) mRNA were both inhibited in the presence of PGE2 or the cAMP analogue (dibutyryl-cAMP), while the anti-inflammatory cytokine IL-10 was highly increased. In contrast, naive CD45RA+T cells were unable to express IL-17 whatever the culture conditions. Naive CD4(+)and CD8(+)T cells were sensitive to the PKA regulatory pathway since they represent a significant source of IL-10 when PBMC were first cultured with ionomycin/PMA in the presence of either PGE2 or db-cAMP. The authors showed that naive cells are highly dependent to their microenvironment, since culture of ionomycin/PMA-activated CD45RA+T cells alone did not result in detectable levels of cytokines even in the presence of PGE2. Results also showed that PGE2 induced quite the same levels of intracellular cAMP in naive and memory cells suggesting that these cell populations are equally sensitive to PGE2. However, we suggest that PGE2 may be more efficient in blocking both IL-17 and IFN-gamma expression in already primed memory T cells, rather than in suppressing naive T cells that could represent a significant source of IL-10. Data suggest that PKA activation pathway plays a critical role in the regulation of cytokine profiles and consequently the functional properties of both human naive and memory CD4(+) and CD8(+)T cells during the immune and inflammatory processes.
在本研究中，作者比较了人初始T细胞和表型明确的记忆T细胞中白细胞介素17（IL-17）的表达情况以及cAMP途径对其的调节作用。我们的数据显示，当外周血单个核细胞先用离子霉素/佛波酯刺激时，IL-17 mRNA在记忆性人外周CD8(+)45RO+T细胞和CD4(+)45RO+T细胞中高表达。记忆性CD8(+)T细胞中IL-17的表达需要辅助信号，因为单独培养离子霉素/佛波酯激活的CD8(+)45RO+T细胞不会导致IL-17表达。相比之下，记忆性CD4(+)T细胞群体似乎更具独立性。在存在前列腺素E2（PGE2）或cAMP类似物（二丁酰-cAMP）的情况下，IL-17和干扰素γ（IFN-γ）mRNA均受到抑制，而抗炎细胞因子IL-10则显著增加。相比之下，无论培养条件如何，初始CD45RA+T细胞均无法表达IL-17。初始CD4(+)和CD8(+)T细胞对PKA调节途径敏感，因为当外周血单个核细胞在存在PGE2或二丁酰-cAMP的情况下先用离子霉素/佛波酯培养时，它们是IL-10的重要来源。作者表明，初始细胞高度依赖其微环境，因为即使在存在PGE2的情况下，单独培养离子霉素/佛波酯激活的CD45RA+T细胞也不会产生可检测水平的细胞因子。结果还表明，PGE2在初始细胞和记忆细胞中诱导的细胞内cAMP水平相当，表明这些细胞群体对PGE2同样敏感。然而，我们认为PGE2可能在阻断已致敏记忆T细胞中IL-17和IFN-γ的表达方面更有效，而不是抑制可能是IL-10重要来源的初始T细胞。数据表明，PKA激活途径在免疫和炎症过程中对人初始和记忆CD4(+)和CD8(+)T细胞的细胞因子谱调节以及功能特性方面起着关键作用。
