Human CD81 directly enhances Th1 and Th2 cell activation, but preferentially induces proliferation of Th2 cells upon long-term stimulation

BMC Immunol. 2003 Feb 19:4:1. doi: 10.1186/1471-2172-4-1. Epub 2003 Feb 19.

Abstract

Background: CD81, a cell-surface protein of the tetraspanin superfamily, has been shown to costimulate T cell activation in murine T cells, and is involved in development of Th2 immune responses in mice.

Results: Here it is shown that stimulation of CD81 on human T cells can enhance T cell activation by antigen or superantigen, causing an increase in the early activation marker CD69, and increasing the number of cytokine-producing and proliferating T cells. Interestingly, CD81 costimulates cytokine production by T cells producing both Th1 and Th2 cytokines. Although human CD81 is highly expressed on non-T as well as T cells, CD81 costimulation appears to act directly on T cells. Pre-incubation of purified T cells with anti-CD81 antibody is sufficient to increase T cell activation, while pre-incubation of non-T cells is not. However, long-term polyclonal stimulation of T cells by anti-CD3 antibody, in the presence of CD81 costimulation, biases T cells towards the production of IL-4 and not IFNgamma. This is accomplished by a preferential proliferation of IL-4-producing cells.

Conclusion: Thus, signalling through CD81 on T cells costimulates both Th1 and Th2 cells, but increases the number of Th2 cells during long-term activation.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Blocking / metabolism
  • Antigens, CD / biosynthesis
  • Antigens, CD / metabolism
  • Antigens, CD / physiology*
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Cell Division / immunology
  • Cell Separation
  • Cross-Linking Reagents / metabolism
  • Cytokines / biosynthesis
  • Humans
  • Interleukin-2 / biosynthesis
  • Lectins, C-Type
  • Lymphocyte Activation / immunology*
  • Membrane Proteins / metabolism
  • Membrane Proteins / physiology*
  • Mice
  • Tetraspanin 28
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism*
  • Th2 Cells / cytology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism*

Substances

  • Antibodies, Blocking
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • CD81 protein, human
  • Cd81 protein, mouse
  • Cross-Linking Reagents
  • Cytokines
  • Interleukin-2
  • Lectins, C-Type
  • Membrane Proteins
  • Tetraspanin 28