IL-2 down-regulates the expression of TCR and TCR-associated surface molecules on CD8(+) T cells.
CD8(+) T cells are known to down-regulate the TCR complex upon ligation with its cognate MHC class I-peptide complex. In the present report, we demonstrate that stimulation of CD8(+) T cells with cytokines also leads to down-regulation of the TCR complex and TCR-associated surface molecules. A significant reduction of TCRalpha beta, CD3, CD8alpha and CD8beta surface expression was observed when CD8(+) T cells were cultured in IL-2 and to a lesser extent in IL-4 or IL-15. The down-regulation was apparent after 2 days of culture and was observed at IL-2 concentrations as low as 10 U/ml. Using TCR transgenic mice, we found that the down-regulation was associated with a decreased affinity of CD8(+) T cells to MHC class I-peptide complexes, as determined by MHC class I tetramer staining. Furthermore, the antigen-specific proliferation of IL-2-pre-activated CD8(+) T cells was significantly reduced compared to naive CD8(+) T cells or to CD8(+) T cells previously stimulated with peptide-pulsed dendritic cells. Moreover, only CD8alpha(high) but not CD8alpha(low) cells sorted from IL-2-activated CD8(+) T cells proliferated in response to specific antigen, although both subsets proliferated equally well to IL-2. Taken together, these data suggest that the down-regulation of TCR components and a subsequent decrease in affinity towards MHC class I-peptide complexes may be a mechanism by which TCR-dependent proliferation of non-specifically activated CD8(+) T cells is avoided.
Kambayashi
T
T
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Assarsson
E
E
Chambers
B J
BJ
Ljunggren
H G
HG
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects*; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D007376:Interleukin-2; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015847:Interleukin-4