Akkaya and Oya et al. demonstrate with in vivo studies that Treg cells suppress the expansion of naive T cells in an antigen-specific manner. Mechanistically, Tregs bound peptide-pulsed dendritic cells (DCs) with more intensity than naive or activated T cells; following contact, Tregs removed the cognate peptide:MHCII complex from the surface of DCs via a process similar to trogocytosis, and thus prevented the activation of naive T cells recognizing the same antigen. Peptide:MHCII complexes with unrelated antigens were not removed from the surface of DCs, and therefore Tregs did not disable the capacity of DCs to activate other T cell responses.
Regulatory T cells (Treg cells) can activate multiple suppressive mechanisms in vitro after activation via the T cell antigen receptor, resulting in antigen-independent suppression. However, it remains unclear whether similar pathways operate in vivo. Here we found that antigen-specific Treg cells activated by dendritic cells (DCs) pulsed with two antigens suppressed conventional naive T cells (Tnaive cells) specific for both cognate antigens and non-cognate antigens in vitro but suppressed only Tnaive cells specific for cognate antigen in vivo. Antigen-specific Treg cells formed strong interactions with DCs, resulting in selective inhibition of the binding of Tnaive cells to cognate antigen yet allowing bystander Tnaive cell access. Strong binding resulted in the removal of the complex of cognate peptide and major histocompatibility complex class II (pMHCII) from the DC surface, reducing the capacity of DCs to present antigen. The enhanced binding of Treg cells to DCs, coupled with their capacity to deplete pMHCII, represents a novel pathway for Treg cell-mediated suppression and may be a mechanism by which Treg cells maintain immune homeostasis.
Author Info: (1) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. billur.akkaya@nih.gov. (2) Laborat
Author Info: (1) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. billur.akkaya@nih.gov. (2) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Department of Rheumatology, Allergy & Clinical Immunology, National Hospital Organization Chiba-East National Hospital, Chiba, Japan. (3) Laboratory of Immunogenetics National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA. (4) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (5) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. University of South Florida Morsani College of Medicine, Tampa, FL, USA. (6) Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (7) Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (8) Department of Rheumatology, Allergy & Clinical Immunology, National Hospital Organization Chiba-East National Hospital, Chiba, Japan. (9) Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Labs, Hamilton, MT, USA. (10) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Rapa Therapeutics, Rockville, MD, USA. (11) Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. eshevach@niaid.nih.gov.
