Mak Tak W, Shahinian Arda, Yoshinaga Steve K, Wakeham Andrew, Boucher Louis-Martin, Pintilie Melania, Duncan Gordon, Gajewska Beata U, Gronski Matthew, Eriksson Urs, Odermatt Bernhard, Ho Alexandra, Bouchard Denis, Whorisky John S, Jordana Manel, Ohashi Pamela S, Pawson Tony, Bladt Friedhelm, Tafuri Anna
Advanced Medical Discovery Institute, and Ontario Cancer Institute, Department of Medical Biophysics , University of Toronto, Toronto, Ontario M5G 2C1, Canada.
Nat Immunol. 2003 Aug;4(8):765-72. doi: 10.1038/ni947. Epub 2003 Jun 29.
Costimulation through the inducible costimulator (ICOS) and its ligand (ICOSL) is essential for T cell-dependent B cell responses, but the cellular and temporal dynamics underlying its in vivo effects are poorly defined. Here we have shown that Icosl(-/-) and Icos(-/-) mice had similar phenotypes and that ICOS-ICOSL costimulation modulated the early but not late phases of IgG1 affinity maturation. Exploiting the adoptive transfer of T or B cells from primed Icosl(-/-) mice, we provided genetic evidence that costimulation through ICOSL was essential for primary but not secondary helper T cell responses and for the control of both T and B cell activities, resulting in T cell-dependent IgG1 production.
通过诱导性共刺激分子（ICOS）及其配体（ICOSL）进行的共刺激对于T细胞依赖性B细胞反应至关重要，但其体内效应背后的细胞和时间动态尚不清楚。在这里，我们表明Icosl(-/-)和Icos(-/-)小鼠具有相似的表型，并且ICOS-ICOSL共刺激调节了IgG1亲和力成熟的早期而非晚期阶段。利用从致敏的Icosl(-/-)小鼠过继转移T细胞或B细胞，我们提供了遗传学证据，即通过ICOSL进行的共刺激对于初始辅助性T细胞反应而非二次辅助性T细胞反应以及对于T细胞和B细胞活性的控制至关重要，从而导致T细胞依赖性IgG1的产生。
