| First Author | Lu Y | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 23 | Pages | 4560-70 |
| PubMed ID | 23047820 | Mgi Jnum | J:190910 |
| Mgi Id | MGI:5450750 | Doi | 10.1182/blood-2012-04-421420 |
| Citation | Lu Y, et al. (2012) Murine regulatory T cells differ from conventional T cells in resisting the CTLA-4 reversal of TCR stop-signal. Blood 120(23):4560-70 |
| abstractText | 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. |
