International Immunology Advance Access first published online on April 11, 2005
This version published online on April 20, 2005
International Immunology, doi:10.1093/intimm/dxh233
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1 Section of Immunobiology, Yale University School of Medicine, 300 Cedar Street, TAC S-569, New Haven, CT 06520, USA; Section of Digestive Diseases, Yale University School of Medicine, 300 Cedar Street, TAC S-569, New Haven, CT 06520, USA
* To whom correspondence should be addressed. Absence of transforming growth factor- Please note: the first name of Leonid Gorelik was spelt incorrectly, the correct spelling appears above.
Received July 26, 2004
Accepted February 4, 2005
Article
TGF-
signaling regulates CD8+ T cell responses to high- and low-affinity TCR interactions
2 Section of Digestive Diseases, Yale University School of Medicine, 300 Cedar Street, TAC S-569, New Haven, CT 06520, USA
3 Biogen Inc., Cambridge, MA, USA
4 Section of Immunobiology, Yale University School of Medicine, 300 Cedar Street, TAC S-569, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, 300 Ceder Street, TAC S569, New Haven CT, 06520, USA
Wajahat Z. Mehal, E-mail: wajahat.mehal{at}yale.edu
Abstract 
(TGF-) 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- 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-1-dominant negative transgene [OT-dominant-negative receptor (DNR)] to investigate the role of TGF- 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- functions in vivo to limit the scale of CD8+ T cell expansion after high-affinity peptide-MHC interactions. TGF- also limits T cell activation to the highest affinity peptide-MHC interactions. The increase in T cell number and activation present in TGF--deficient and TGF- DNR-expressing mice may be due to the loss of these two phenomena.
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