Lineage and signal strength determine the inhibitory effect of transforming growth factor beta1 (TGF-beta1) on human antigen-specific Th1 and Th2 memory cells.
TGF-beta1 is a pleotrophic cytokine playing an important role in immune regulation. The impact of TGF-beta1 on immune function is determined by the cell type and the microenvironment. CD4+ T cells exemplify this, by responding to TGF-beta1 in heterogeneous ways based on their level of maturation and state of differentiation. TGF-beta1 leads to suppression of proliferation and cytokine production of naive T cells and influences the outcome of T cell differentiation. In mice, the response of memory T cells to TGF-beta1 is determined by the lineage of the cells. TGF-beta1 causes decreased proliferation of Th1 cells but has little effect on the proliferation of Th2 cells. Here we examined the effect of TGF-beta1 on human Th1 and Th2 memory T cells and show that proliferation of Th1 clones are inhibited by TGF-beta1, whereas Th2 cells are not. Furthermore the sensitivity of individual Th1 clones to TGF-beta1 is linked to the level of activation achieved in culture, but these differences cannot be explained by T cell receptor (TCR) affinity alone. Together this demonstrates that the human T cell response to TGF-beta1 is determined by the environment in which an immune response takes place and the previous immune experience of the cells involved.
Holzer
Ursula
U
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA. ursula.holzer@med.uni-tuebingen.de
Rieck
Mary
M
Buckner
Jane Hoyt
JH
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D019070:Cell Lineage; D004330:Drosophila; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4