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Altered proximal T cell receptor (TCR) signaling in human CD4+CD25+ regulatory T cells
Author(s) -
Tsang Julia YuenShan,
Camara Niels Olsen Saraiva,
Eren Efrem,
Schneider Helga,
Rudd Christopher,
Lombardi Giovanna,
Lechler Robert
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0605344
Subject(s) - biology , t cell receptor , phosphorylation , il 2 receptor , microbiology and biotechnology , signal transduction , tyrosine phosphorylation , cd3 , t cell , jurkat cells , zap70 , immunoreceptor tyrosine based activation motif , peripheral tolerance , cd8 , immunology , immune system , sh2 domain
CD4+CD25+ regulatory T cells play an important role in peripheral tolerance. Upon T cell receptor (TCR)‐mediated activation, the cells fail to proliferate but are induced to have a suppressor function. The intracellular signaling events that lead to their responses have not been elucidated. In this study, we have examined the proximal TCR signaling events in freshly isolated human CD4+CD25+ regulatory T cells after TCR ligation. In contrast to CD4+CD25– T cells, TCR ligation of CD4+CD25+ regulatory T cells by anti‐CD3 cross‐linking resulted in a lower calcium influx and extracellular signal‐regulated kinase 1/2 phosphorylation. Examination of the CD3ζ chain phosphorylation status indicated that CD4+CD25+ regulatory T cells have poor phosphorylation of the protein and consequently, reduced recruitment of ζ‐associated protein‐70 to the TCR immunoreceptor tyrosine motif. The adaptor protein, Src homology 2 domain‐containing leukocyte phosphoprotein of 76 kDa, which relays signals to downstream signaling components, also showed reduced phosphorylation, which correlated with reduced VAV guanine nucleotide exchange factors association. Consistent with other findings, the defect is accompanied with impaired actin cap formation, implicating a failure of actin remodeling of the cells. Together, our results demonstrate that CD4+CD25+ regulatory T cells have altered TCR proximal signaling pathways, which could be critical for inducing the distinct behavior of these cells.