International Immunology Advance Access originally published online on April 11, 2005
International Immunology 2005 17(5):531-538; doi:10.1093/intimm/dxh233
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TGF-ß signaling regulates CD8+ T cell responses to high- and low-affinity TCR interactions
1 Section of Immunobiology and 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 Howard Hughes Medical Institute, Yale University, 300 Ceder Street, TAC S569, New Haven CT, 06520, USA
Correspondence to: W. Z. Mehal; E-mail: wajahat.mehal{at}yale.edu
Absence of transforming growth factor-ß (TGF-ß) 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-ß 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-ß1-dominant negative transgene [OT-dominant-negative receptor (DNR)] to investigate the role of TGF-ß 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-ß functions in vivo to limit the scale of CD8+ T cell expansion after high-affinity peptide–MHC interactions. TGF-ß also limits T cell activation to the highest affinity peptide–MHC interactions. The increase in T cell number and activation present in TGF-ß-deficient and TGF-ß DNR-expressing mice may be due to the loss of these two phenomena.
Keywords: antigen/peptides/epitopes, cellular activation, rodent, T lymphocytes
Transmitting editor: M. Feldmann
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