Burdach S, Shatsky M, Wagenhorst B, Levitt L
Division of Hematology, Stanford University Medical Center, CA 94305.
Blood. 1988 Aug;72(2):770-5.
We examined the role of the T-cell antigen CD2 in the regulation of erythropoiesis by the lymphokine cascade. T-cell interleukin-2 (IL-2) receptors (p55) were induced via triggering of the antigen receptor-associated CD3 epitope. Before CD3 triggering T cells were preincubated with a CD2-blocking (Leu-5b) or isotype control antibody. T-cell pellets were employed during incubation to facilitate interaction between T-cell LFA-3 and CD2. CD2 blockade caused a 66% to 79% inhibition of p55 expression after three to six days of culture with IL-2. Next we assessed the effect of CD2 blockade on IL-2. Next we assessed the effect of CD2 blockade on IL-2-induced inhibition of BFU-E in autologous cocultures containing CD3-triggered T cells. IL-2 caused a dose-dependent inhibition (52% to 92%) of BFU-E in the presence but not in the absence of CD3-triggered T cells. T-cell CD2 blockade prior to CD3 triggering caused a 65% to 87% abrogation of IL-2-induced inhibition of BFU-E at 10 to 10(2) U/mL IL-2. Preincubation of CD3-triggered T cells with isotype control antibody had no effect on IL-2-induced erythroid inhibition. Day 3 supernatants from CD3-triggered T cells or CD2-blocked, CD3-triggered T cells established in the presence of IL-2 were next assessed for modulation of BFU-E. CD3-triggered T-cell supernatants caused a 77% +/- 9% inhibition of BFU-E. Blockade of CD2 caused a 95% abrogation of T-cell-mediated BFU-E inhibition. In addition, CD2 blockade reduced interferon-gamma (IF gamma) release (84 to 128 U/mL) from CD3-triggered T cells by 81% at day 3 of culture. In control experiments, the addition of IF gamma-neutralizing monoclonal antibody to CD3-triggered T-cell supernatant established in the presence of IL-2 caused 75% abrogation of IL-2 inhibition of BFU-E. We conclude that blockade of the CD2 T-cell determinant induces down modulation of (a) T-cell p55 IL-2 receptor expression, (b) IL-2-induced inhibition of BFU-E, and (c) IL-2-induced marrow T-cell IF gamma release. These data suggest that the T-cell CD2 determinant can exert a regulatory effect on the control of erythropoiesis by the lymphokine cascade.
我们研究了T细胞抗原CD2在淋巴因子级联反应对红细胞生成调节中的作用。通过触发与抗原受体相关的CD3表位，诱导T细胞白细胞介素-2（IL-2）受体（p55）。在CD3触发之前，将T细胞与CD2阻断抗体（Leu-5b）或同型对照抗体进行预孵育。在孵育过程中使用T细胞沉淀以促进T细胞淋巴细胞功能相关抗原-3（LFA-3）与CD2之间的相互作用。用IL-2培养三到六天后，CD2阻断导致p55表达受到66%至79%的抑制。接下来，我们评估了CD2阻断对IL-2的影响。接下来，我们评估了在含有CD3触发T细胞的自体共培养物中，CD2阻断对IL-2诱导的爆式红系集落形成单位（BFU-E）抑制的影响。在有而非无CD3触发T细胞存在的情况下，IL-2对BFU-E产生剂量依赖性抑制（52%至92%）。在CD3触发之前阻断T细胞CD2导致在10至10(2) U/mL IL-2时，IL-2诱导的BFU-E抑制被65%至87%消除。用同型对照抗体预孵育CD3触发的T细胞对IL-2诱导的红系抑制无影响。接下来评估在IL-2存在下建立的CD3触发T细胞或CD2阻断的CD3触发T细胞培养第3天的上清液对BFU-E的调节作用。CD3触发的T细胞上清液导致BFU-E受到77%±9%的抑制。阻断CD2导致T细胞介导的BFU-E抑制被95%消除。此外，在培养第3天，CD2阻断使CD3触发T细胞的干扰素-γ（IFγ）释放（84至128 U/mL）减少81%。在对照实验中，向在IL-2存在下建立的CD3触发T细胞上清液中加入IFγ中和单克隆抗体导致IL-2对BFU-E的抑制被75%消除。我们得出结论，阻断CD2 T细胞决定簇可诱导（a）T细胞p55 IL-2受体表达下调，（b）IL-2诱导的BFU-E抑制下调，以及（c）IL-2诱导的骨髓T细胞IFγ释放下调。这些数据表明，T细胞CD2决定簇可对淋巴因子级联反应对红细胞生成的控制发挥调节作用。
