Lin S-J, Cheng P-J, Hsiao S-S
Division of Asthma, Allergy and Rheumatology, Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University, Taoyuan, Taiwan.
Bone Marrow Transplant. 2006 May;37(9):881-7. doi: 10.1038/sj.bmt.1705348.
Autologous transfer of anti-CD3/anti-CD28 (CD3/CD28)-activated CD4(+) T cells may benefit patients receiving autologous stem cell transplant with severe CD4 lymphopenia. Interleukin (IL)-15, an IL-2-like cytokine that promotes T cell survival may enhance immune reconstitution in conjunction with adoptive immunotherapy. We investigated the effect of IL-15 on effector and regulatory function of CD3/CD28-activated CD4(+) T cells. IL-15 upregulated CD45RO and CD25 whereas it down regulated CD62L expression of CD3/CD28-stimulated CD4(+) T cells. Both type 1 (IFN-gamma, tumor necrosis factor (TNF)-alpha) and type 2 (IL-5 and IL-10) production by CD3/CD28-activated CD4(+) T cells was further enhanced by IL-15. Co-culture experiments revealed that CD3/CD28-activated CD4(+) T cells down regulated proliferation of autologous peripheral blood lymphocytes (PBLs) and CD8(+) PBL subsets upon TCR ligation, a contact-dependent effect that was further enhanced by pretreatment with IL-15. Flow cytometric analysis of cell mixture with carboxyfluorescein diacetate succinimidyl ester and Annexin-V-PE staining revealed that CD3/CD28+IL-15-activated CD4(+) T cells showed increased apoptosis over CD4(+) T cells stimulated with CD3/CD28 alone. Taken together, pretreatment of CD3/CD28-activated CD4(+) T cells with IL-15 may increase regulatory function but may aggravate activation-induced apoptosis of CD3/CD28 CD4(+) T cells.
抗CD3/抗CD28（CD3/CD28）激活的CD4(+) T细胞的自体转移可能使接受自体干细胞移植且伴有严重CD4淋巴细胞减少的患者受益。白细胞介素（IL）-15是一种促进T细胞存活的IL-2样细胞因子，与过继性免疫疗法联合使用时可能增强免疫重建。我们研究了IL-15对CD3/CD28激活的CD4(+) T细胞的效应和调节功能的影响。IL-15上调CD45RO和CD25，而下调CD3/CD28刺激的CD4(+) T细胞的CD62L表达。IL-15进一步增强了CD3/CD28激活的CD4(+) T细胞产生1型（干扰素-γ、肿瘤坏死因子（TNF）-α）和2型（IL-5和IL-10）细胞因子的能力。共培养实验表明，CD3/CD28激活的CD4(+) T细胞在TCR连接后下调自体外周血淋巴细胞（PBL）和CD8(+) PBL亚群的增殖，这是一种接触依赖性效应，用IL-15预处理可进一步增强。用羧基荧光素二乙酸琥珀酰亚胺酯和膜联蛋白-V-PE染色对细胞混合物进行流式细胞术分析显示，与单独用CD3/CD28刺激的CD4(+) T细胞相比，CD3/CD28 + IL-15激活的CD4(+) T细胞凋亡增加。综上所述，用IL-15预处理CD3/CD28激活的CD4(+) T细胞可能增加调节功能，但可能加重CD3/CD28 CD4(+) T细胞的激活诱导凋亡。
