DY determinants, possibly associated with novel class II molecules, stimulate autoreactive CD4+ T cells with suppressive activity.
DY determinants, possibly associated with novel class II molecules, stimulate autoreactive CD4+ T cells with suppressive activity.
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DOI：
10.1084/jem.167.2.243
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发表时间：
1988-02-01
影响因子：
15.3
通讯作者：
WERNET, P
中科院分区：
文献类型：
--
作者：
PAWELEC, G;FERNANDEZ, N;BROCKER, T;SCHNEIDER, EM;FESTENSTEIN, H;WERNET, P
从HLA-DR-、Dw-、DQ-匹配的同种异体MLC中分离的一组T细胞克隆（TCC）被发现在用携带广泛的I类或II类特异性的细胞刺激时自主增殖。这种明显不受限制的增殖相对较弱，并且刺激细胞的上清液中仅存在低水平的IL-2。自体以及同种异体PBMC和B淋巴母细胞样细胞系（B-LCL）能够刺激这些克隆，这些克隆也被抑制性TCC再刺激，但不被辅助TCC再刺激。此外，这些克隆显示出不寻常的自刺激特性。mAb抑制实验表明，II类或II类限制性抗原参与刺激。因此，与多基因座产物反应的某些“宽”mAb（TU 39、SG 520）抑制这些试剂的活化，但与DR（TU 34、TU 37、L243、Q2/70、SG 157）、DQ（TU 22、SPV-L3、Leu 10）或DP（B7/21）或这些mAb的混合物更特异性反应的那些mAb都不能这样做。从连续免疫沉淀实验的证据表明，单克隆抗体TU 39结合II类分子以外的DR，DQ，和DP的TCC和B-LCL，因此，它建议，这种推定的新的II类分子可能携带这些自身反应性克隆的刺激决定簇。DY反应性克隆缺乏B细胞的辅助活性，但介导对T细胞增殖反应的有效抑制活性，其不受反应细胞的HLA类型的限制。在正常PBMC中通过这些克隆以及通过独立的抑制性克隆诱导抑制活性，所述独立的抑制性克隆也仅通过mAb TU 39抑制。这些发现导致提出DY反应性自刺激细胞可能构成自我维持抑制回路，其活性水平将主要由微环境中IL-2的可用性调节。
A set of T cell clones (TCC) isolated from HLA-DR-, Dw-, DQ-matched allogeneic MLCs was found to proliferate autonomously when stimulated with cells carrying a wide range of class I or II specificities. This apparently unrestricted proliferation was relatively weak, and only low levels of IL-2 were present in the supernatants of stimulated cells. Autologous as well as allogeneic PBMC and B lymphoblastoid cell lines (B-LCL) were capable of stimulating such clones, which were also restimulated by suppressive, but not by helper, TCC. Moreover, such clones displayed the unusual property of autostimulation. mAb inhibition experiments suggested that class II- or class II-restricted antigens were involved in stimulation. Thus, certain "broad" mAbs (TU39, SG520) reacting with multiple locus products inhibited activation of these reagents, but none of those reacting more specifically with DR (TU34, TU37, L243, Q2/70, SG157), DQ (TU22, SPV- L3, Leu 10), or DP (B7/21), or mixtures of these mAbs, were able to do so. Evidence from sequential immunoprecipitation experiments suggested that mAb TU39 bound class II-like molecules other than DR, DQ, and DP on TCC and B-LCL, and it is therefore proposed that such putative novel class II-like molecules may carry the stimulating determinants for these autoreactive clones. DY-reactive clones lacked helper activity for B cells but mediated potent suppressive activity on T cell proliferative responses that was not restricted by the HLA type of the responding cells. Suppressive activity was induced in normal PBMC by such clones, as well as by independent suppressive clones, which was also inhibited only by mAb TU39. These findings lead to the proposal that DY-reactive autostimulatory cells may constitute a self- maintaining suppressive circuit, the level of activity of which would be regulated primarily by the availability of IL-2 in the microenvironment.
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影响因子：
5.4
作者：
PAWELEC, G;SCHNEIDER, EM;WERNET, P
通讯作者：
WERNET, P
影响因子：
2.7
作者：
PAWELEC, G;SCHNEIDER, EM;WERNET, P
通讯作者：
WERNET, P
影响因子：
2.7
作者：
PAWELEC, G;WERNET, P;SCHNEIDER, EM
通讯作者：
SCHNEIDER, EM
DOI：
10.1016/0161-5890(78)90070-6
发表时间：
1978-01-01
期刊：
IMMUNOCHEMISTRY
影响因子：
--
作者：
EY, PL;PROWSE, SJ;JENKIN, CR
通讯作者：
JENKIN, CR
DOI：
10.1016/0006-291x(72)90581-5
发表时间：
1972-01-01
影响因子：
3.1
作者：
HAYMAN, MJ;CRUMPTON, MJ
通讯作者：
CRUMPTON, MJ