Murine regulatory T cells differ from conventional T cells in resisting the CTLA-4 reversal of TCR stop-signal.

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

Blood

journal_title

Blood

authors

Lu Y,Schneider H,Rudd CE

doi

10.1182/blood-2012-04-421420

subject

Has Abstract

pub_date

2012-11-29 00:00:00

pages

4560-70

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2012-04-421420

journal_volume

120

pub_type

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