LAG-3 expression defines a subset of CD4+ CD25highFoxp3+ regulatory T cells that are expanded at tumor sites

C Camisaschi, C Casati, F Rini, M Perego… - The Journal of …, 2010 - journals.aai.org
C Camisaschi, C Casati, F Rini, M Perego, A De Filippo, F Triebel, G Parmiani, F Belli…
The Journal of Immunology, 2010journals.aai.org
Human natural regulatory CD4+ T cells comprise 5–10% of peripheral CD4+ T cells. They
constitutively express the IL-2Rα− chain (CD25) and the nuclear transcription Foxp3. These
cells are heterogeneous and contain discrete subsets with distinct phenotypes and
functions. Studies in mice report that LAG-3 has a complex role in T cell homeostasis and is
expressed in CD4+ CD25+ T regulatory cells. In this study, we explored the expression of
LAG-3 in human CD4+ T cells and found that LAG-3 identifies a discrete subset of CD4+ …
Abstract
Human natural regulatory CD4+ T cells comprise 5–10% of peripheral CD4+ T cells. They constitutively express the IL-2Rα− chain (CD25) and the nuclear transcription Foxp3. These cells are heterogeneous and contain discrete subsets with distinct phenotypes and functions. Studies in mice report that LAG-3 has a complex role in T cell homeostasis and is expressed in CD4+ CD25+ T regulatory cells. In this study, we explored the expression of LAG-3 in human CD4+ T cells and found that LAG-3 identifies a discrete subset of CD4+ CD25 high Foxp3+ T cells. This CD4+ CD25 high Foxp3+ LAG-3+ population is preferentially expanded in the PBMCs of patients with cancer, in lymphocytes of tumor-invaded lymph nodes and in lymphocytes infiltrating visceral metastasis. Ex vivo analysis showed that CD4+ CD25 high Foxp3+ LAG-3+ T cells are functionally active cells that release the immunosuppressive cytokines IL-10 and TGF-β1, but not IL-2. An in vitro suppression assay using CD4+ CD25 high LAG-3+ T cells sorted from in vitro expanded CD4+ CD25 high regulatory T cells showed that this subset of cells is endowed with potent suppressor activity that requires cell-to-cell contact. Our data show that LAG-3 defines an active CD4+ CD25 high Foxp3+ regulatory T cell subset whose frequency is enhanced in the PBMCs of patients with cancer and is expanded at tumor sites.
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