Hillemeyer Peter, White Michelle D, Pascual David W
Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA.
Cell Immunol. 2002 Feb;215(2):173-85. doi: 10.1016/s0008-8749(02)00024-2.
Past studies have described the serendipitous appearance of peripheral CD4(+)CD8(+) double-positive (DP) T cells in both humans and nonhuman primates usually following a viral infection or resulting from a malignancy. However, understanding the role of DP T cells has been hampered by the lack of their reproducible generation. Herein, we describe DP T cells produced after a single intratracheal or intranasal dose of recombinant adenovirus 2 or 5 vector into mice. In a time-dependent fashion, DP T cells localized only in the deep cervical lymph nodes but not in the lungs or in any of the respiratory lymph nodes. These DP T cells were TCR(alpha)beta(+) and CD8(alpha)beta(+), but not TCR(gamma)delta(+) nor CD8(alpha)alpha(+), suggesting that these cells are unrelated to intestinally derived DP T cells. Upon co-stimulation with anti-CD3 and anti-CD28, DP T cells showed increased expression of VLA-1, VLA-2, and CD69, and were more effective than CD4(+) T cells in T helper cell activity, as evidenced by increased IgA, IgG, and IgM production. Such co-stimulation also favored the production of IFN-gamma and IL-10 where CD4(+) T cells were more inclined to produce IFN-gamma and IL-2.
过去的研究描述了人类和非人灵长类动物外周CD4(+)CD8(+)双阳性（DP）T细胞的偶然出现，通常是在病毒感染后或由恶性肿瘤导致。然而，由于缺乏可重复性的产生方式，对DP T细胞作用的理解受到了阻碍。在此，我们描述了经气管内或鼻内单次给予重组腺病毒2型或5型载体后在小鼠体内产生的DP T细胞。DP T细胞以时间依赖性方式仅定位于颈深部淋巴结，而不在肺或任何呼吸道淋巴结中。这些DP T细胞是TCR(α)β(+)和CD8(α)β(+)，但不是TCR(γ)δ(+)也不是CD8(α)α(+)，这表明这些细胞与肠道来源的DP T细胞无关。在用抗CD3和抗CD28共同刺激后，DP T细胞显示VLA-1、VLA-2和CD69的表达增加，并且在辅助性T细胞活性方面比CD4(+) T细胞更有效，这通过增加的IgA、IgG和IgM产生得到证明。这种共同刺激也有利于IFN-γ和IL-10的产生，而CD4(+) T细胞更倾向于产生IFN-γ和IL-2。
