Flechner E R, Freudenthal P S, Kaplan G, Steinman R M
Rockefeller University, New York, New York.
Cell Immunol. 1988 Jan;111(1):183-95. doi: 10.1016/0008-8749(88)90062-7.
Experimental conditions have been developed to detect the efficient interaction of antigen-presenting cells and antigen-specific CD4+ T lymphocytes early in the human primary mixed-leukocyte reaction (MLR). When monocytes are depleted from the stimulator population, it is evident that small numbers of allogeneic dendritic cells form multicellular aggregates with responsive T cells. B cells and monocytes in allogeneic stimulator populations do not appear to form aggregates in the first 2 days of the MLR. Upon return to culture, most of the lymphocytes that have clustered with dendritic cells become IL-2 responsive, proliferating lymphoblasts. The nonclustered cells exhibit little growth, while mixtures of clusters and nonclusters proliferate comparably to clusters alone. Cluster-derived lymphocytes respond rapidly to rechallenge with foreign leukocytes from the original donor but are greater than 90% depleted of reactivity to other "third party" donors. Nonclustered lymphocytes, in contrast, are greater than 90% depleted in specific reactivity but respond normally to third party. Therefore antigen-specific (alloreactive) resting CD4+ lymphocytes efficiently and selectively aggregate with dendritic cells. Dendritic-T-cell aggregates represent a stable microenvironment in which the MLR begins and might be useful in the experimental analysis of early events in the sensitization phase of cell-mediated immunity in man.
已开发出实验条件,以在人类初次混合淋巴细胞反应(MLR)早期检测抗原呈递细胞与抗原特异性CD4 + T淋巴细胞的有效相互作用。当从刺激细胞群体中去除单核细胞时,很明显少量的同种异体树突状细胞会与反应性T细胞形成多细胞聚集体。在MLR的前两天,同种异体刺激细胞群体中的B细胞和单核细胞似乎不会形成聚集体。重新培养后,大多数与树突状细胞聚集的淋巴细胞会对IL-2产生反应,增殖为淋巴母细胞。未聚集的细胞几乎不生长,而聚集细胞与未聚集细胞的混合物与单独的聚集细胞增殖程度相当。源自聚集体的淋巴细胞对来自原始供体的外来白细胞再次刺激反应迅速,但对其他“第三方”供体的反应性降低超过90%。相比之下,未聚集的淋巴细胞特异性反应性降低超过90%,但对第三方的反应正常。因此,抗原特异性(同种异体反应性)静止CD4 +淋巴细胞有效地且选择性地与树突状细胞聚集。树突状细胞 - T细胞聚集体代表了一个稳定的微环境,MLR在此环境中开始,可能有助于对人类细胞介导免疫致敏阶段早期事件进行实验分析。