CTLA-4 and Tolerance: The Biochemical Point of View

Shunsuke Chikuma, Jeffrey A. Bluestone

研究成果: Review article査読

67 被引用数 (Scopus)

抄録

Potentially autoreactive T cells that escape negative selection in the thymus must be strictly controlled in the periphery to avoid autoimmune disease. The most robust regulatory process controlling autoreactivity is mediated by the CTLA-4-B7 pathway. The critical homeostasis mediated by CTLA-4 was proven using monoclonal antibodies and genetically disrupted CTLA-4 knockout mice that develop polyclonal lymphocyte activation and proliferation leading to massively enlarged lymph nodes and spleen and fatal multiorgan lymphocytic infiltrates. CTLA-4 ligation following T-cell activation downregulates cytokine production and cell-cycle progression, however, the proximal biochemical basis for robust T-cell regulation remains unclear. In this review, we summarize studies supporting a dynamic role for CTLA-4 at the immunological synapse leading to direct attenuation of early cell signals. A model is proposed based on these observations, which proposes that CTLA-4 may, in fact, function under some circumstances in a ligand-independent manner.

本文言語English
ページ(範囲)241-253
ページ数13
ジャーナルImmunologic Research
28
3
DOI
出版ステータスPublished - 2003
外部発表はい

ASJC Scopus subject areas

  • 免疫学

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