Antigen-specific targeting of CD8+ T cells with receptor-modified T lymphocytes.
Antigen-specific targeting of CD8+ T cells with receptor-modified T lymphocytes.
复制标题
使用受体修饰的 T 淋巴细胞对 CD8 T 细胞进行抗原特异性靶向。
DOI：
10.1038/sj.gt.3301932
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发表时间：
2003
期刊：
影响因子：
5.1
通讯作者：
Geiger,TL
中科院分区：
文献类型：
--
作者：
Nguyen,P;Geiger,TL
Chimeric receptors that link ligand recognition domains, such as antibody Fv fragments, with TCR signaling domains can redirect T lymphocytes against MHC-unrestricted targets. Such receptor-modified T lymphocytes have shown promise in the treatment of infectious diseases and cancer. We hypothesized that receptor-modified T lymphocytes may also be designed to target antigen-specific T cells. We synthesized chimeric receptors consisting of the extracellular and transmembrane domains of the class I MHC H-2K b molecule linked to the signaling domains of either TCR-ζ, CD28 and ζ, or CD28, ζ, and lck. T lymphocytes modified to express these receptors and pulsed with antigenic peptide specifically killed precursor CTL. Cytolysis was efficient, even at effector: target ratios of less than one, and specific, selectively killing antigen-specific precursor CTL among a mixed population of T cells. Cytolysis required activation of the receptor-modified T cells, and did not occur with a signaling-deficient chimeric receptor. In contrast to precursor CTL, differentiated CTL proved resistant to lysis by the receptor-modified T cells. These data demonstrate the feasibility of redirecting T lymphocytes against antigen-specific T cells. Receptor-modified T cells expressing chimeric MHC receptors have potential application in autoimmune and alloimmune diseases.
