Immunosuppression in man: suppression by macrophages can be mediated by interactions with regulatory T cells.
Immunosuppression in man: suppression by macrophages can be mediated by interactions with regulatory T cells.
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人类的免疫抑制：巨噬细胞的抑制可以通过与调节性 T 细胞的相互作用介导。
作者：
J. Stobo
该实验室先前的数据表明，一些真菌感染患者体内和体外 T 细胞功能的严重缺陷反映了免疫抑制力量的存在。对这种免疫抑制变得明显所需的细胞相互作用的研究揭示了以下内容。患者的巨噬细胞在体外释放出一种可溶性物质 (SM)3，该物质能够抑制正常 T 细胞对有丝分裂原和抗原的胚细胞反应。然而，并非所有 T 细胞都同样容易受到其抑制作用的影响。将正常 PBMC 在培养液中孵育 7 天，产生了一群培养的 T 细胞，其反应性不能被 SM 抑制。结合研究表明，这种“抵抗”并不反映培养的 T 细胞与 SM 相互作用的能力发生任何总体改变。相反，它反映了 SM 介导其抑制作用所需的 T 细胞亚群的功能缺失。发现在低密度、新鲜、自体 T 细胞存在的情况下，SM 能够抑制培养的 T 细胞的反应性，这一发现证明了这一点。 SM 和低密度 T 细胞之间的类似相互作用似乎是 SM 抑制新鲜非培养 PBMC 中 T 依赖性反应所必需的。因此，从新鲜正常PBMC中去除低密度T产生高密度T，其反应性不被SM抑制。这些研究被解释为表明所研究患者的免疫抑制并不反映抑制性巨噬细胞和反应性 T 细胞之间的直接相互作用。相反，它代表了一种间接相互作用，巨噬细胞可以通过这种相互作用产生或增强活性抑制性 T 细胞。
Previous data from this laboratory indicated that profound defects of in vivo and in vitro T cell function noted in some patients with fungal infection reflected the presence of immunosuppressive forces. Investigation of the cellular interactions required for this immunosuppression to become manifest revealed the following. Patients' macrophages liberated, in vitro, a soluble material (SM)3 capable of inhibiting the blastogenic response of normal T cells to mitogens and antigens. However, not all T cells were equally susceptible to its suppressive effect. Incubation of normal PBMC in culture fluid for 7 days yielded a population of cultured T cells whose reactivity could not be inhibited by SM. Binding studies indicated that this “resistance” did not reflect any gross alterations in the ability of cultured T cells to interact with SM. Rather, it reflected the functional deletion of a subpopulation of T cells required for SM to mediate its suppressive effect. This was demonstrated by the finding that in the presence of low density, fresh, autologous T cells, SM was capable of suppressing the reactivity of cultured T cells. Similar interactions between SM and low density T cells appeared to be required for SM to inhibit T-dependent responses among fresh noncultured PBMC. Thus, removal of low density T from fresh normal PBMC yielded high density T whose reactivity was not suppressed by SM. These studies are interpreted as indicating that immunosuppression in the patients studied does not reflect direct interactions between suppressive macrophages and responding T cells. Instead, it represents an indirect interaction whereby macrophages may generate or potentiate active suppressive T cells.