期刊
BLOOD
卷 112, 期 1, 页码 120-130出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-09-114181
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资金
- NCI NIH HHS [CA-16042, P30 CA016042] Funding Source: Medline
- NIAID NIH HHS [P30 AI028697, 2-T32-AI-07323, T32 AI07323-15, AI07126-30, AI-28697, T32 AI007126, T32 AI007323] Funding Source: Medline
- NIGMS NIH HHS [R01 GM063281, R01 GM63281] Funding Source: Medline
- PHS HHS [R01A1056155] Funding Source: Medline
During thymocyte development, the T-cell receptor (TCR) can discriminate major histocompatibility complex (MHC)/peptide ligands over a narrow range of affinities and translate subtle differences into functional fate decisions. How small differences in TCR input are translated into absolute differences in functional output is unclear. We examined the effects of galectin-1 ablation in the context of class-I-restricted thymocyte development. Galectin-1 expression opposed TCR partial agonist-driven positive selection, but promoted TCR agonist-driven negative selection of conventional CD8(+) T cells. Galectin-1 expression also promoted TCR agonist-driven CD8 alpha alpha intestinal intraepithelial lymphocytes (IEL) development. Recombinant galectin-1 enhanced TCR binding to agonist/MHC complexes and promoted a negative-selection-signaling signature, reflected in intensified rapid and transient extracellular signal-regulated kinase (ERK) activation. In contrast, galectin-1 expression antagonized ERK activity in thymocytes undergoing positive selection. We propose that galectin-1 aids in discriminating TCR-directed fate decisions by promoting TCR binding to agonist/MHC complexes and enforcing agonist-driven signals, while opposing partial-agonist signals. In this way, galectin-1 widens the distinction between TCR-directed functional fate cues.
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