Levine B L, Ueda Y, Craighead N, Huang M L, June C H
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD, USA.
Int Immunol. 1995 Jun;7(6):891-904. doi: 10.1093/intimm/7.6.891.
The interaction of CD28 and its ligands is critical for antigen-induced T cell activation. Recent studies have demonstrated the existence of at least two members of the B7 receptor family. In this report, the co-stimulatory signals provided by CD80 (B7-1) or CD86 (B7-2) were compared to CD28 ligation by mAb. We demonstrate that the kinetics of induction of T cell proliferation after anti-CD3 stimulation was similar regardless of the form of co-stimulation. Similarly, B7-1 and B7-2 could both maintain long-term expansion of CD4 cells. The co-stimulatory effects of both B7-1 and B7-2 were dependent on CD28 cross-linking, based on complete inhibition of proliferation by CD28 antibody Fab fragments. Co-stimulation with B7-1 and B7-2 induced high levels of cytokine secretion by resting T cells, and the effects of B7-1 and B7-2 could not be distinguished. This conclusion is based on analysis of the initial activation of CD28+ T cells, as well as T cell subpopulations consisting of CD4+ and CD8+ T cells. Both B7-1 and B7-2 could elicit IL-4 secretion from CD4+ T cells while anti-CD28 antibody induced substantially less IL-4 secretion. Furthermore, both B7-1 and B7-2 could stimulate high levels of IFN-gamma and IL-4 from CD4+CD45RO+ cells, while neither B7 receptor could co-stimulate IFN-gamma and IL-4 secretion from CD4+CD45RA+ T cells. B7-1 and B7-2 could, however, co-stimulate CD4+CD45RA+ T cells to secrete IL-2. By contrast, when previously activated T cells were tested, re-stimulation of CD4+ T cell blasts with B7-1 or B7-2 resulted in higher secretion of IL-4 and IL-5 than anti-CD28, while re-stimulation with anti-CD28 antibody maintained a higher level of secretion of IL-2 and IFN-gamma than B7-1 or B7-2. These observations may have important implications because they suggest that the manner of CD28 ligation can be a critical determinant in the development of cytokine secretion that corresponds to Th1- and Th2-like patterns of differentiation. Together these observations suggest that there are no intrinsic differences between B7-1 and B7-2 in their ability to co-stimulate the populations of cells that we have tested.
CD28与其配体的相互作用对于抗原诱导的T细胞活化至关重要。最近的研究表明，B7受体家族至少存在两个成员。在本报告中，将CD80（B7-1）或CD86（B7-2）提供的共刺激信号与单克隆抗体介导的CD28连接进行了比较。我们证明，无论共刺激形式如何，抗CD3刺激后T细胞增殖诱导的动力学相似。同样，B7-1和B7-2都能维持CD4细胞的长期扩增。基于CD28抗体Fab片段对增殖的完全抑制，B7-1和B7-2的共刺激作用均依赖于CD28交联。用B7-1和B7-2进行共刺激可诱导静息T细胞分泌高水平的细胞因子，且无法区分B7-1和B7-2的作用。这一结论基于对CD28+T细胞初始活化以及由CD4+和CD8+T细胞组成的T细胞亚群的分析。B7-1和B7-2均可诱导CD4+T细胞分泌IL-4，而抗CD28抗体诱导的IL-4分泌则少得多。此外，B7-1和B7-2均可刺激CD4+CD45RO+细胞分泌高水平的IFN-γ和IL-4，而两种B7受体均不能共刺激CD4+CD45RA+T细胞分泌IFN-γ和IL-4。然而，B7-1和B7-2均可共刺激CD4+CD45RA+T细胞分泌IL-2。相比之下，当测试先前活化的T细胞时，用B7-1或B
