Thorson J A, Smith K M, Gomez F, Naumann P W, Kemp J D
Department of Pathology, University of Iowa College of Medicine, Iowa City 52242.
Cell Immunol. 1991 Apr 15;134(1):126-37. doi: 10.1016/0008-8749(91)90336-a.
TH1 and TH2 helper T cell clones have been studied with respect to their sensitivity to inhibition of DNA synthesis by an IgG anti-transferrin receptor antibody (ATRA), the iron chelator deferoxamine, and the combination of the two reagents. TH1 clones are very sensitive to ATRA-mediated inhibition of DNA synthesis while TH2 clones are very resistant, but both TH1 and TH2 clones show significant down-modulation of surface transferrin receptors after ATRA exposure. TH2 clones exhibit larger chelatable iron storage pools than TH1 clones, however, and even partial chelation of TH2 cell storage iron does not fully convert a TH2 clone to the ATRA sensitivity pattern of a TH1 clone. It is therefore proposed that the greater resistance of TH2 clones to ATRA mediated inhibition derives from the combined effects of larger and less labile iron storage pools. These studies provide novel evidence indicating that nonuniform iron metabolism can exist within the T cell compartment and thus raise questions as to why such differences exist and how they can be integrated into models of the T cell activation process. These studies also suggest that the cell-mediated immune response in vivo, which is known to be sensitive to iron deficiency, may be evoked by effector cells which resemble TH1 clones insofar as iron metabolism is concerned.
针对TH1和TH2辅助性T细胞克隆，研究了它们对IgG抗转铁蛋白受体抗体（ATRA）、铁螯合剂去铁胺以及这两种试剂组合抑制DNA合成的敏感性。TH1克隆对ATRA介导的DNA合成抑制非常敏感，而TH2克隆则非常耐受，但在暴露于ATRA后，TH1和TH2克隆的表面转铁蛋白受体均表现出显著的下调。然而，TH2克隆比TH1克隆表现出更大的可螯合铁储存池，并且即使TH2细胞储存铁的部分螯合也不能使TH2克隆完全转变为具有TH1克隆的ATRA敏感性模式。因此，有人提出TH2克隆对ATRA介导的抑制具有更大的抗性源于更大且更稳定的铁储存池的综合作用。这些研究提供了新的证据，表明T细胞区室内可能存在不均匀的铁代谢，从而引发了关于为何存在这种差异以及如何将它们整合到T细胞激活过程模型中的问题。这些研究还表明，体内已知对缺铁敏感的细胞介导免疫反应，可能由在铁代谢方面类似于TH1克隆的效应细胞引发。
