Stout R D, Suttles J, Persiani D M, Bakke O
Cell Immunol. 1986 Aug;101(1):105-21. doi: 10.1016/0008-8749(86)90190-5.
Adherent layers of macrophages (M phi-c) generated in vitro from splenic precursors inhibit lymphoproliferative responses to mitogen and to alloantigen without inhibiting the production of interleukin-2 (IL-2). Analysis of spleen cells stimulated for 48 hr in the presence of M phi-c indicated that both blastogenesis (increased cell mass) and expression of IL-2 receptors (7D4 determinants) were reduced. Analysis of BrdU incorporation (frequency of S-phase cells) and total cellular DNA revealed that the M phi-c inhibited the progression from G1 to S phase of cell cycle. The M phi-c not only inhibited the proliferative response to alloantigen but also prevented the generation of alloreactive cytotoxic T cells. The M phi-c were shown not to inhibit CTL responses by eliminating the stimulators or by inactivating precursors or inducing suppressors. The M phi-c were affecting the induction of CTL activity since the M phi-c did not affect the expression of cytolytic activity by activated CTL. The M phi-c did inhibit the proliferation of the activated CTL, suggesting that although cytolytic activity can be expressed in G1 phase of cell cycle, the activation of cytolytic activity in CTL-P may require a G1 to S phase transition. The cells recovered from 5-day MLC incubated in the presence of M phi-c were fully capable of generating a subsequent CTL response. This is in contrast to cells recovered from unstimulated cultures (no M phi-c) which have lost the ability to generate CTL responses. The M phi-c therefore prevent the generation of CTL responses in a totally reversible fashion, so as to allow activation and proliferation of CTL-P which have been removed from the influence of the M phi-c. These observations are discussed in the context of the currently hypothesized role of tissue macrophages in microenvironmental regulation.
从脾前体细胞体外生成的巨噬细胞贴壁层（M phi-c）可抑制对丝裂原和同种异体抗原的淋巴细胞增殖反应，而不抑制白细胞介素-2（IL-2）的产生。在M phi-c存在下刺激48小时的脾细胞分析表明，细胞增殖（细胞质量增加）和IL-2受体（7D4决定簇）的表达均降低。对溴脱氧尿苷掺入（S期细胞频率）和总细胞DNA的分析表明，M phi-c抑制细胞周期从G1期到S期的进程。M phi-c不仅抑制对同种异体抗原的增殖反应，还阻止同种反应性细胞毒性T细胞的产生。已表明M phi-c不是通过消除刺激物、使前体细胞失活或诱导抑制物来抑制细胞毒性T淋巴细胞（CTL）反应。M phi-c影响CTL活性的诱导，因为M phi-c不影响活化的CTL的溶细胞活性表达。M phi-c确实抑制活化的CTL的增殖，这表明尽管溶细胞活性可在细胞周期的G1期表达，但CTL前体细胞（CTL-P）中溶细胞活性的激活可能需要从G1期到S期的转变。在M phi-c存在下培养5天的混合淋巴细胞培养物（MLC）中回收的细胞完全能够产生随后的CTL反应。这与从未刺激培养物（无M phi-c）中回收的细胞形成对比，后者已失去产生CTL反应的能力。因此，M phi-c以完全可逆的方式阻止CTL反应的产生，以便允许已从M phi-c影响中去除的CTL-P的激活和增殖。在目前假设的组织巨噬细胞在微环境调节中的作用背景下讨论了这些观察结果。
