Rauschmayr-Kopp T, Williams I R, Borriello F, Sharpe A H, Kupper T S
Harvard Skin Disease Research Center, Department of Medicine, Boston, MA 02115, USA.
Eur J Immunol. 1998 Dec;28(12):4221-7. doi: 10.1002/(SICI)1521-4141(199812)28:12<4221::AID-IMMU4221>3.0.CO;2-M.
Productive interactions between B7-1 and B7-2 costimulatory molecules on dendritic cells (DC) and CD28 on T cells are thought to be critical for successful antigen presentation. Epicutaneous application of haptens induces both contact hypersensitivity (CHS), an inflammatory cutaneous response mediated by CD8+ T cells, and an anti-hapten antibody response mediated by CD4+ helper T cells. The role of B7 costimulation in the immune response to oxazolone (Ox) was analyzed using mice lacking either B7-1 (B7-1-/-), B7-2 (B7-2-/-), or both (Db-/-) of these costimulatory molecules. The absence of both B7-1 and B7-2 results in diminished CHS. This inhibition is largely overcome at higher hapten sensitizing doses indicating the presence of compensatory pathways. In contrast, anti-Ox IgG1 and IgG2a responses were not detected in the absence of both B7-1 and B7-2, even at high sensitizing doses, indicating an obligatory role of B7 costimulation in IgG class switching. B7-1 and B7-2 have overlapping functions in both CHS responses and anti-hapten response. B7-2-/- mice demonstrated a modestly reduced CHS response only at very low doses of Ox (0.05%), but responded normally at higher Ox doses, and B7-1-/- mice had CHS responses indistinguishable from those of wild-type mice. Similarly, anti-Ox IgG responses were comparable in wild-type, B7-1-/- and B7-2-/- mice. Taken together, these studies reveal distinct roles for B7 costimulation in response to epicutaneous antigens with an obligatory role for IgG class switching and an important, but nonessential role for CHS responses.
树突状细胞（DC）上的共刺激分子B7-1和B7-2与T细胞上的CD28之间的有效相互作用被认为对成功的抗原呈递至关重要。经皮应用半抗原可诱导接触性超敏反应（CHS），这是一种由CD8⁺T细胞介导的炎症性皮肤反应，以及由CD4⁺辅助性T细胞介导的抗半抗原抗体反应。使用缺乏这些共刺激分子中的B7-1（B7-1⁻/⁻）、B7-2（B7-2⁻/⁻）或两者（Db⁻/⁻）的小鼠，分析了B7共刺激在对恶唑酮（Ox）免疫反应中的作用。B7-1和B7-2均缺失会导致CHS减弱。在较高的半抗原致敏剂量下，这种抑制作用在很大程度上被克服，表明存在补偿途径。相比之下，即使在高致敏剂量下，在B7-1和B7-2均缺失的情况下也未检测到抗Ox IgG1和IgG2a反应，这表明B7共刺激在IgG类别转换中起必不可少的作用。B7-1和B7-2在CHS反应和抗半抗原反应中具有重叠功能。B7-2⁻/⁻小鼠仅在非常低剂量的Ox（0.05%）下表现出适度降低的CHS反应，但在较高的Ox剂量下反应正常，而B7-1⁻/⁻小鼠的CHS反应与野生型小鼠无异。同样，野生型、B7-1⁻/⁻和B7-2⁻/⁻小鼠的抗Ox IgG反应相当。综上所述，这些研究揭示了B7共刺激在对经皮抗原反应中的不同作用，其中IgG类别转换起必不可少的作用，而CHS反应起重要但非必需的作用。
