TY - JOUR
T1 - Identification of a CD4+ T cell line with Treg-like activity
AU - Ho, Thai H.
AU - Pfeffer, Kirsten
AU - Weiss, Glen J.
AU - Ruiz, Yvette
AU - Lake, Douglas F.
N1 - Publisher Copyright:
© 2022 American Society for Histocompatibility and Immunogenetics
PY - 2022/4
Y1 - 2022/4
N2 - Regulatory T cells (Tregs) suppress adaptive immunity and inflammation. Although they play a role in suppressing anti-tumor responses, development of therapeutics that target Tregs is limited by their low abundance, heterogeneity, and lack of specific cell surface markers. We isolated human PBMC-derived CD4+ CD25high Foxp3+ Tregs and demonstrate they suppress stimulated CD4+ PBMCs in a cell contact-dependent manner. Because it is not possible to functionally characterize cells after intracellular Foxp3 staining, we identified a human T cell line, MoT, as a model of human Foxp3+ Tregs. Unlike Jurkat T cells, MoT cells share common surface markers consistent with human PBMC-derived Tregs such as: CD4, CD25, GITR, LAG-3, PD-L1, CCR4. PBMC-derived Tregs and MoT cells, but not Jurkat cells, inhibited proliferation of human CD4+ PBMCs in a ratio-dependent manner. Transwell membrane separation prevented suppression of stimulated CD4+ PBMC proliferation by MoT cells and Tregs, suggesting cell–cell contact is required for suppressive activity. Blocking antibodies against PD-L1, LAG-3, GITR, CCR4, HLA-DR, or CTLA-4 did not reverse the suppressive activity. We show that human PBMC-derived Tregs and MoT cells suppress stimulated CD4+ PBMCs in a cell contact-dependent manner, suggesting that a Foxp3+ Treg population suppresses immune responses by an uncharacterized cell contact-dependent mechanism.
AB - Regulatory T cells (Tregs) suppress adaptive immunity and inflammation. Although they play a role in suppressing anti-tumor responses, development of therapeutics that target Tregs is limited by their low abundance, heterogeneity, and lack of specific cell surface markers. We isolated human PBMC-derived CD4+ CD25high Foxp3+ Tregs and demonstrate they suppress stimulated CD4+ PBMCs in a cell contact-dependent manner. Because it is not possible to functionally characterize cells after intracellular Foxp3 staining, we identified a human T cell line, MoT, as a model of human Foxp3+ Tregs. Unlike Jurkat T cells, MoT cells share common surface markers consistent with human PBMC-derived Tregs such as: CD4, CD25, GITR, LAG-3, PD-L1, CCR4. PBMC-derived Tregs and MoT cells, but not Jurkat cells, inhibited proliferation of human CD4+ PBMCs in a ratio-dependent manner. Transwell membrane separation prevented suppression of stimulated CD4+ PBMC proliferation by MoT cells and Tregs, suggesting cell–cell contact is required for suppressive activity. Blocking antibodies against PD-L1, LAG-3, GITR, CCR4, HLA-DR, or CTLA-4 did not reverse the suppressive activity. We show that human PBMC-derived Tregs and MoT cells suppress stimulated CD4+ PBMCs in a cell contact-dependent manner, suggesting that a Foxp3+ Treg population suppresses immune responses by an uncharacterized cell contact-dependent mechanism.
KW - CFSE T cell suppression assays
KW - Contact-dependent suppression
KW - Regulatory T cells
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U2 - 10.1016/j.humimm.2022.01.008
DO - 10.1016/j.humimm.2022.01.008
M3 - Article
C2 - 35094878
AN - SCOPUS:85123727569
SN - 0198-8859
VL - 83
SP - 281
EP - 294
JO - Human Immunology
JF - Human Immunology
IS - 4
ER -