CD86 and CD80 differentially modulate the suppressive function of human regulatory T cells

J Immunol. 2004 Mar 1;172(5):2778-84. doi: 10.4049/jimmunol.172.5.2778.

Abstract

Regulatory T cells (Treg) are important in maintaining tolerance to self tissues. As both CD28 and CTLA-4 molecules are implicated in the function of Treg, we investigated the ability of their two natural ligands, CD80 and CD86, to influence the Treg-suppressive capacity. During T cell responses to alloantigens expressed on dendritic cells, we observed that Abs against CD86 potently enhanced suppression by CD4(+)CD25(+) Treg. In contrast, blocking CD80 enhanced proliferative responses by impairing Treg suppression. Intriguingly, the relative expression levels of CD80 and CD86 on dendritic cells are modulated during progression from an immature to a mature state, and this correlates with the ability of Treg to suppress responses. Our data show that CD80 and CD86 have opposing functions through CD28 and CTLA-4 on Treg, an observation that has significant implications for manipulation of immune responses and tolerance in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / pharmacology
  • Antigens, CD / immunology
  • Antigens, CD / physiology*
  • Antigens, Differentiation / physiology
  • B7-1 Antigen / physiology*
  • B7-2 Antigen
  • CD28 Antigens / physiology
  • CTLA-4 Antigen
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Isoantigens / biosynthesis
  • Isoantigens / physiology
  • Lymphocyte Culture Test, Mixed
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Receptors, Interleukin-2 / biosynthesis
  • Self Tolerance / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunosuppressive Agents
  • Isoantigens
  • Membrane Glycoproteins
  • Receptors, Interleukin-2