Abstract:
:Productive T-cell immunity requires both the activation and the migration of specific T cells to the antigenic tissue. The costimulatory molecule CD28 plays an essential role in the initiation of T-cell-mediated immunity. We investigated the possibility that CD28 may also regulate migration of primed T cells to target tissue. In vitro, CD28-mediated signals enhanced T-cell transendothelial migration, integrin clustering, and integrin-mediated migration. In vivo, T cells bearing a mutation in the CD28 cytoplasmic domain, which abrogates PI3K activation, displayed normal clonal expansion but defective localization to antigenic sites following antigenic rechallenge. Importantly, antibody-mediated CD28 stimulation led to unregulated memory T-cell migration to extra-lymphoid tissue, which occurred independently of T-cell receptor (TCR)-derived signals and homing-receptor expression. Finally, we provide evidence that CD28- and CTLA-4-mediated signals exert opposite effects on T-cell trafficking in vivo. These findings highlight a novel physiologic function of CD28 that has crucial implications for the therapeutic manipulation of this and other costimulatory molecules.
journal_name
Bloodjournal_title
Bloodauthors
Mirenda V,Jarmin SJ,David R,Dyson J,Scott D,Gu Y,Lechler RI,Okkenhaug K,Marelli-Berg FMdoi
10.1182/blood-2006-10-050724subject
Has Abstractpub_date
2007-04-01 00:00:00pages
2968-77issue
7eissn
0006-4971issn
1528-0020pii
blood-2006-10-050724journal_volume
109pub_type
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