Knop J, Taborski B, DeMaeyer-Guignard J
J Immunol. 1987 Jun 1;138(11):3684-7.
The T suppressor (Ts) cell response in contact sensitivity is preferentially inhibited by murine interferon-alpha, beta (IFN-alpha, beta) in vivo. Previous studies in vivo have suggested that IFN exerts its effect directly on the Ts subpopulation rather than through an effect on antigen-presenting macrophages. Nevertheless, the mechanism of this selective blockade remained unclear. To better define the mechanism(s) of inhibition of suppression by IFN-alpha, beta, we determined whether IFN acted on lymphocytes, macrophages, or both. Antigen-specific T effector cells of delayed-type hypersensitivity (TDH) and Ts cells were induced in vitro by co-culture of spleen lymphocytes with bone marrow-derived antigen-presenting macrophages (BM-MA) pulse-labeled with 2,4-dinitrobenzene sulfonate (DNBSO3). TDH or Ts activity was demonstrated by transfer of the lymphocytes into naive recipient BALB/c mice after 3 days of culture. BM-MA cultured for 5 to 7 days (BM-MA d5-7) before labeling preferentially activated TDH cells (Thy-1+, Lyt-1+2-); 10- to 14-day-old BM-MA (BM-MA d10) induced Ts cells (Thy-1+, Lyt-2+), as previously shown. Treatment of the spleen lymphocyte suspension with pure mouse IFN-alpha, beta at a dose of 10(3) U/10(8) cells completely blocked the induction of Ts cells but had no effect on the induction of TDH cells. Pretreatment of the antigen-presenting BM-MA for 24 hr with IFN (10(2) U/3 X 10(5) cells) had no effect on the induction of Ts and TDH cells. Cultivation of lymphocytes on a DNP-BM-MA d6 monolayer did not result in the induction of Ts cells; however, in the presence of a goat anti-murine IFN-alpha, beta antibody, Ts cells were induced. This finding indicates that the spontaneous release of IFN-alpha, beta in those cultures prevented the induction of Ts cells. These results confirm our previous observation that Ts cells are more easily blocked by IFN-alpha, beta than TDH cells, and demonstrate that IFN affects the Ts subpopulation not via modulation of the antigen-presenting macrophages. IFN-alpha, beta-producing, antigen-presenting, or accessory cells may therefore prevent the activation of this type of Ts cell.
在接触性敏感反应中，小鼠α、β干扰素（IFN-α、β）在体内优先抑制T抑制（Ts）细胞反应。以往的体内研究表明，IFN直接作用于Ts亚群，而非通过对抗抗原呈递巨噬细胞起作用。然而，这种选择性阻断的机制仍不清楚。为了更好地确定IFN-α、β抑制抑制作用的机制，我们确定了IFN是作用于淋巴细胞、巨噬细胞还是两者都起作用。通过将脾淋巴细胞与用2,4 -二硝基苯磺酸盐（DNBSO3）脉冲标记的骨髓来源抗原呈递巨噬细胞（BM - MA）共培养，在体外诱导迟发型超敏反应（TDH）的抗原特异性T效应细胞和Ts细胞。培养3天后，将淋巴细胞转移到未致敏的受体BALB / c小鼠中，以证明TDH或Ts活性。在标记前培养5至7天的BM - MA（BM - MA d5 - 7）优先激活TDH细胞（Thy - 1 +，Lyt - 1 + 2 -）；如先前所示，10至14日龄的BM - MA（BM - MA d10）诱导Ts细胞（Thy - 1 +，Lyt - 2 +）。用剂量为10³ U / 10⁸细胞的纯小鼠IFN - α、β处理脾淋巴细胞悬液可完全阻断Ts细胞的诱导，但对TDH细胞的诱导没有影响。用IFN（10² U / 3×10⁵细胞）预处理抗原呈递BM - MA 24小时，对Ts和TDH细胞的诱导没有影响。在DNP - BM - MA d6单层上培养淋巴细胞不会诱导Ts细胞；然而，在存在山羊抗小鼠IFN - α、β抗体的情况下，可诱导Ts细胞。这一发现表明，那些培养物中IFN - α、β的自发释放阻止了Ts细胞的诱导。这些结果证实了我们之前的观察，即Ts细胞比TDH细胞更容易被IFN - α、β阻断，并证明IFN不是通过调节抗原呈递巨噬细胞来影响Ts亚群。因此，产生IFN - α、β的抗原呈递细胞或辅助细胞可能会阻止这类Ts细胞的激活。
