Abstract:
:CTLA-4 inhibits T-cell activation and protects against the development of autoimmunity. We and others previously showed that the coreceptor can induce T-cell motility and shorten dwell times with dendritic cells (DCs). However, it has been unclear whether this property of CTLA-4 affects both conventional T cells (Tconvs) and regulatory T cells (Tregs). Here, we report that CTLA-4 had significantly more potent effects on the motility and contact times of Tconvs than Tregs. This was shown firstly by anti-CTLA-4 reversal of the anti-CD3 stop-signal on FoxP3-negative cells at concentrations that had no effect on FoxP3-positive Tregs. Secondly, the presence of CTLA-4 reduced the contact times of DO11.10 x CD4(+)CD25(-) Tconvs, but not DO11.10 x CD4(+)CD25(+) Tregs, with OVA peptide presenting DCs in lymph nodes. Thirdly, blocking of CTLA-4 with anti-CTLA-4 Fab increased the contact times of Tconvs, but not Tregs with DCs. By contrast, the presence of CD28 in a comparison of Cd28(-/-) and Cd28(+/+) DO11.10 T cells had no detectable effect on the contact times of either Tconvs or Tregs with DCs. Our findings identify for the first time a mechanistic explanation to account for CTLA-4-negative regulation of Tconv cells but not Tregs in immune responses.
journal_name
Bloodjournal_title
Bloodauthors
Lu Y,Schneider H,Rudd CEdoi
10.1182/blood-2012-04-421420subject
Has Abstractpub_date
2012-11-29 00:00:00pages
4560-70issue
23eissn
0006-4971issn
1528-0020pii
blood-2012-04-421420journal_volume
120pub_type
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