Wyss-Coray T, Mauri-Hellweg D, Baumann K, Bettens F, Grunow R, Pichler W J
Institute of Clinical Immunology, Inselspital, Switzerland.
Eur J Immunol. 1993 Sep;23(9):2175-80. doi: 10.1002/eji.1830230919.
The B cell antigen B7 delivers a strong co-stimulatory signal for the activation of T cells by binding to its ligands CD28 and CTLA4. Here we demonstrate the surface expression of the B7 molecule on activated human T cells in vitro and under certain conditions in vivo and its functional importance in T-T cell interactions. B7 was detected by flow cytometry on antigen-specific CD4+ and allospecific CD8+ cloned T cells from different donors with anti-B7 monoclonal antibody (mAb) or a soluble CTLA4-C gamma 1 chimera molecule and by reverse transcription-polymerase chain reactions. The expression of B7 was up-regulated following restimulation of the T cell clones and peaked after 7-9 days. Moreover, we show that the B7 molecule on T cells is functionally involved in T-T cell interactions: mAb to CD28 and the CTLA4-Ig fusion protein could inhibit the proliferation of specific T cell clones in response to T cells as antigen-presenting cells (APC) or the proliferation of peripheral blood mononuclear cells in a primary allostimulation with activated T cells as stimulator cells. Finally, we found that B7 can be expressed on freshly isolated circulating T cells since in a preliminary study with a limited number of patients, B7 was present on a subset of CD3+ cells. B7 was expressed on activated T cells (CD4+ and CD8+) of certain human immunodeficiency virus (HIV)-infected individuals (0.5-20% B7+CD8+ cells) or some patients with autoimmune diseases whereas CD3+ cells of healthy individuals did not express B7. The coexpression of major histocompatibility complex class II molecules and B7 may be relevant for the capacity of activated T cells to function as APC. The expression of B7 on T cells in vivo in autoimmune diseases and in HIV infection may be important for a better understanding of these diseases.
B细胞抗原B7通过与配体CD28和CTLA4结合，为T细胞的激活传递强大的共刺激信号。在此，我们证明了B7分子在体外活化的人T细胞上以及在某些体内条件下的表面表达，及其在T-T细胞相互作用中的功能重要性。通过流式细胞术，使用抗B7单克隆抗体（mAb）或可溶性CTLA4-Cγ1嵌合分子，在来自不同供体的抗原特异性CD4⁺和同种异体特异性CD8⁺克隆T细胞上检测到B7，并通过逆转录-聚合酶链反应进行检测。T细胞克隆再次刺激后，B7的表达上调，并在7-9天后达到峰值。此外，我们表明T细胞上的B7分子在功能上参与T-T细胞相互作用：抗CD28单克隆抗体和CTLA4-Ig融合蛋白可抑制特异性T细胞克隆对作为抗原呈递细胞（APC）的T细胞的增殖反应，或抑制外周血单个核细胞在以活化T细胞作为刺激细胞的初次同种异体刺激中的增殖。最后，我们发现B7可以在新鲜分离的循环T细胞上表达，因为在对有限数量患者的初步研究中，B7存在于一部分CD3⁺细胞上。在某些人类免疫缺陷病毒（HIV）感染个体（0.5%-20%的B7⁺CD8⁺细胞）或一些自身免疫性疾病患者的活化T细胞（CD4⁺和CD8⁺）上表达B7，而健康个体的CD3⁺细胞不表达B7。主要组织相容性复合体II类分子和B7的共表达可能与活化T细胞作为APC的功能能力相关。B7在自身免疫性疾病和HIV感染的体内T细胞上的表达，可能对更好地理解这些疾病具有重要意义。
