| First Author | Mehal WZ | Year | 2005 |
| Journal | Int Immunol | Volume | 17 |
| Issue | 5 | Pages | 531-8 |
| PubMed ID | 15824070 | Mgi Jnum | J:98437 |
| Mgi Id | MGI:3578475 | Doi | 10.1093/intimm/dxh233 |
| Citation | Mehal WZ, et al. (2005) TGF-{beta} signaling regulates CD8+ T cell responses to high- and low-affinity TCR interactions. Int Immunol 17(5):531-8 |
| abstractText | Absence of transforming growth factor-beta (TGF-beta) signaling to T cells in mice results in an increase in T cell numbers, an activated CD44 high, CD69-, CD25- T cell phenotype and a T cell-mediated injury to many organs. It is not known if such T cell activation in the absence of TGF-beta signaling is spontaneous or due to aberrant T cell responses to a physiological stimulus. We used adoptive transfer of CD8+ T cells from mice double transgenic for the OT-1 TCR and the TGF-beta1-dominant negative transgene [OT-dominant-negative receptor (DNR)] to investigate the role of TGF-beta in regulating CD8+ T cell activation in vivo. The activation and expansion of single-transgenic OT and double-transgenic OT-DNR cells to oral antigens, high-affinity and low-affinity peptides were indistinguishable. Activation with high-affinity peptide and CFA however resulted in greater expansion of OT-DNR cells in comparison to OT cells. Low-affinity peptide and adjuvant did not result in OT cell activation or expansion but results in up-regulation of CD44 on OT-DNR cells. These data show that TGF-beta functions in vivo to limit the scale of CD8+ T cell expansion after high-affinity peptide-MHC interactions. TGF-beta also limits T cell activation to the highest affinity peptide-MHC interactions. The increase in T cell number and activation present in TGF-beta-deficient and TGF-beta DNR-expressing mice may be due to the loss of these two phenomena. |
