| Literature DB >> 17964663 |
Jos Downey1, Andrew Smith, Helga Schneider, Nancy Hogg, Christopher E Rudd.
Abstract
CTLA-4 is a co-receptor that plays a pivotal role in regulating the threshold for T-cell activation. We recently reported that CTLA-4 ligation can over-ride the stop-signal induced by anti-CD3 ligation [Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al. Reversal of the TCR stop-signal by CTLA-4. Science 2006;313:1972]. While these studies compared CTLA-4 positive and negative T-cells from normal mice, little is known regarding the behaviour of T-cells from diseased Ctla4 deficient mice with auto-proliferative disease. In this study, we show that while activated wild-type and Ctla-4-/- T-cells have similar rates of motility, Ctla-4-/- T-cells show a marked resistance to the induction of a stop-signal by anti-CD3 ligation. By contrast, T-cells from normal mice and CD28 deficient mice underwent a normal slowing of motility in response to anti-CD3 ligation. Our findings identify a fundamental difference between normal versus CTLA-4-/- T-cells from diseased mice in the regulation of motility by anti-CD3 ligation. This dysregulation of motility may contribute to the tissue infiltration and the autoimmune disorder observed in Ctla-4-/- mice.Entities:
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Year: 2007 PMID： 17964663 PMCID： PMC4186962 DOI： 10.1016/j.imlet.2007.09.004
Source DB: PubMed Journal: Immunol Lett ISSN： 0165-2478 Impact factor: 3.685