Wu J Y, Gardner B H, Kushner N N, Pozzi L A, Kensil C R, Cloutier P A, Coughlin R T, Newman M J
Cambridge Biotech Corporation, Worcester, Massachusetts 01605.
Cell Immunol. 1994 Apr 1;154(1):393-406. doi: 10.1006/cimm.1994.1086.
The in vivo and in vitro accessory cell requirements of class I major histocompatability complex (MHC) antigen-restricted cytotoxic T-lymphocyte (CTL) responses were determined using cell-depletion experiments coupled with active immunizations using ovalbumin (OVA) as the immunogen and saponin adjuvant (QS-21). To paralyze macrophage activity in vivo, C57BL/6 mice were treated with particulate silica or carrageenan. In vivo depletion of helper T-lymphocytes was accomplished by treatment with GK1.5 rat monoclonal antibody, which is specific for the murine CD4 antigen, and by genetic depletion of class II MHC antigens. Following treatments, the mice were immunized with formulations containing OVA alone or mixed with QS-21 saponin adjuvant, which induces MHC class I antigen-restricted CTL responses. In vivo treatment to paralyze macrophages abrogated these CTL responses but not antigen-specific antibody or lymphocyte proliferative responses. Depletion of CD4+ T-lymphocytes had no effect on CTL responses but significantly reduced proliferation and antibody responses. In vitro depletion and reconstitution experiments were done to compare the contributions of different antigen-presenting cells (APC), specifically dendritic cells (DC) and macrophages. Again, the requirement for macrophages was absolute but there was no indication that DC were involved. These data suggest that antigen processing and presentation functions are critical to the induction of CTL and that they are a function of macrophages but that CD4+ helper T-lymphocyte functions are not required.
利用细胞清除实验，结合以卵清蛋白（OVA）作为免疫原和皂苷佐剂（QS-21）进行主动免疫，确定了I类主要组织相容性复合体（MHC）抗原限制性细胞毒性T淋巴细胞（CTL）反应在体内和体外对辅助细胞的需求。为了在体内使巨噬细胞活性麻痹，用颗粒状二氧化硅或角叉菜胶处理C57BL/6小鼠。通过用对鼠CD4抗原具有特异性的GK1.5大鼠单克隆抗体处理以及通过II类MHC抗原的基因清除来实现体内辅助性T淋巴细胞的清除。处理后，用单独含有OVA或与QS-21皂苷佐剂混合的制剂免疫小鼠，该佐剂可诱导MHC I类抗原限制性CTL反应。在体内使巨噬细胞麻痹的处理消除了这些CTL反应，但未消除抗原特异性抗体或淋巴细胞增殖反应。CD4 + T淋巴细胞的清除对CTL反应没有影响，但显著降低了增殖和抗体反应。进行了体外清除和重建实验，以比较不同抗原呈递细胞（APC），特别是树突状细胞（DC）和巨噬细胞的作用。同样，对巨噬细胞的需求是绝对的，但没有迹象表明DC参与其中。这些数据表明，抗原加工和呈递功能对于CTL的诱导至关重要，并且它们是巨噬细胞的功能，但不需要CD4 +辅助性T淋巴细胞功能。
