Butler Jared J, Cochran Jennifer, Ward Natalie, Hoskin David W
Department of Microbiology, Dalhousie University, Halifax, Canada.
Am J Transplant. 2002 Mar;2(3):215-22. doi: 10.1034/j.1600-6143.2002.20305.x.
T-cell activation requires both T-cell receptor signaling and a costimulatory signal provided by CD28 which enhances and prolongs interleukin-2 (IL-2) production. To determine the effect of cyclosporine A (CsA) on constitutive and activation-induced CD28 expression, mouse T cells were exposed to CsA (0.1 microM) in the absence or presence of anti-CD3 monoclonal antibody (mAb). CD28 expression was then determined by flow cytometry. CsA treatment prevented activation-induced CD28 expression but did not affect constitutive CD28 expression. Inhibition of inducible CD28 expression by CsA was not rapidly reversible, requiring 48h of restimulation in the absence of CsA for CD28 expression to return to control levels. T cells activated in the presence of combined anti-IL-2 and anti-CD25 mAb (both 10 microg/mL) also exhibited reduced CD28 expression, suggesting that activation-induced CD28 expression is, at least in part, an IL-2-dependent process. However, the inhibitory effect of CsA on activation-induced CD28 expression was maintained in the presence of exogenous IL-2 (250 U/mL). We conclude that CsA, by inhibiting activation-induced expression of costimulatory CD28 molecules by T lymphocytes, may interfere with the ability of CD28 to provide an optimal costimulatory signal for sustained IL-2 production following T-cell activation.
T细胞活化需要T细胞受体信号传导以及由CD28提供的共刺激信号，该信号可增强并延长白细胞介素-2（IL-2）的产生。为了确定环孢素A（CsA）对组成性和活化诱导的CD28表达的影响，将小鼠T细胞在不存在或存在抗CD3单克隆抗体（mAb）的情况下暴露于CsA（0.1微摩尔）。然后通过流式细胞术确定CD28表达。CsA处理可防止活化诱导的CD28表达，但不影响组成性CD28表达。CsA对诱导性CD28表达的抑制作用不是快速可逆的，需要在不存在CsA的情况下进行48小时的再刺激，以使CD28表达恢复到对照水平。在联合使用抗IL-2和抗CD25 mAb（均为10微克/毫升）的情况下活化的T细胞也表现出CD28表达降低，这表明活化诱导的CD28表达至少部分是一个IL-2依赖性过程。然而，在存在外源性IL-2（250单位/毫升）的情况下，CsA对活化诱导的CD28表达的抑制作用仍然存在。我们得出结论，CsA通过抑制T淋巴细胞对共刺激CD28分子的活化诱导表达，可能会干扰CD28在T细胞活化后为持续的IL-2产生提供最佳共刺激信号的能力。
