CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy.
CD2 is involved in maintenance and reversal of human alloantigen-specific clonal anergy.
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DOI：
10.1084/jem.180.5.1665
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发表时间：
1994-11-01
期刊：
影响因子：
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通讯作者：
Nadler LM
中科院分区：
文献类型：
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作者：
Boussiotis VA;Freeman GJ;Griffin JD;Gray GS;Gribben JG;Nadler LM
诱导和维持T细胞对特异性同种异体抗原的无反应性状态将对人类器官移植具有重要意义。使用人类组织相容性白细胞抗原DR 7特异性辅助性T细胞克隆，我们证明了阻断B7家族的共刺激分子足以诱导同种异体抗原特异性T细胞克隆无能。失能细胞对同种异体抗原和多种共刺激分子，包括B7-1、B7-2、细胞间粘附分子-1（ICAM-1）和淋巴细胞功能相关分子（LFA）-3不应答。然而，在外源性白细胞介素（IL）-2培养至少7天后，无反应的细胞可以在LFA-3的存在下对同种异体抗原作出反应。LFA-3共刺激随后在先前不充分的共刺激信号存在下恢复对同种异体抗原的反应性。CD 2 R表位的表达在无能细胞上下调，并且在IL-2培养7天后恢复。CD 2 R的丧失与无反应细胞对LFA-3的无反应能力在时间上相关。这些结果表明，除了阻断B7家族成员外，抑制CD 2和可能逆转无反应性的其他共刺激途径对于维持长期的同种异体抗原特异性耐受是必要的。
Induction and maintenance of a state of T cell unresponsiveness to specific alloantigen would have significant implications for human organ transplantation. Using human histocompatibility leukocyte antigen DR7-specific helper T cell clones, we demonstrate that blockade of the B7 family of costimulatory molecules is sufficient to induce alloantigen-specific T cell clonal anergy. Anergized cells do not respond to alloantigen and a variety of costimulatory molecules, including B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1), and lymphocyte function-associated molecule (LFA)-3. However, after culture in exogenous interleukin (IL)-2 for at least 7 d, anergized cells can respond to alloantigen in the presence of LFA-3. LFA-3 costimulation subsequently restores responsiveness to alloantigen in the presence of previously insufficient costimulatory signals. Expression of CD2R epitope is downregulated on anergic cells and is restored after 7 d of IL-2 culture. The loss of the CD2R is temporally associated with the inability of anergized cells to respond to LFA-3. These results suggest that in addition to blockade of B7 family members, inhibition of CD2 and, potentially, other costimulatory pathways that might reverse anergy will be necessary to maintain prolonged alloantigen-specific tolerance.