The suppression of delayed-type hypersensitivity by CD8+ regulatory T cells requires interferon-gamma.

Abstract

CD8(+) regulatory (suppressor) T cells are induced by complex cellular pathways in the spleens of mice that have received an injection of antigen into the anterior chamber (AC) of an eye, an immune-privileged site. Although these CD8(+) regulatory T cells perform an antigen-specific regulatory function for an immune response to self and non-self antigens, the mechanisms of the activation or function of these regulatory cells are not clear. Here, we describe a novel mechanism for the activation of splenic CD8(+) regulatory T cells induced by injection of antigen into the AC. Immunization of mice with trinitrophenyl and bovine serum albumin (TNP-BSA) amplified AC-induced splenic CD8(+) regulatory T cells that suppressed the initiation of contact sensitivity when transferred to immunized, challenged mice. These CD8(+) regulatory T cells were produced independently of perforin, indicating that they are not canonical cytotoxic T cells. Fas ligand (FasL)-deficient CD8(+) regulatory T-cell function was rescued by inclusion of exogenous interferon-gamma (IFN-gamma), demonstrating that the expression of FasL by CD8(+) regulatory T cells was dispensable, but IFN-gamma was not. Ultimately, we demonstrated that the generation of these CD8(+) regulatory T cells occurred independently of IFN-gamma, but their suppressor function required IFN-gamma receptor stimulation.

• Authors: Robert E Cone, Xingya Li, Roshanak Sharafieh, James O'Rourke, Anthony T Vella
• Journal: Immunology (Immunology) Vol. 120 Issue 1 Pg. 112-9 (Jan 2007) ISSN: 0019-2805 [Print] England
• PMID: 17052246 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fas Ligand Protein
• Fasl protein, mouse
• Membrane Glycoproteins
• Pore Forming Cytotoxic Proteins
• trinitrophenyl-bovine serum albumin
• Perforin
• Serum Albumin, Bovine
• Interferon-gamma

Topics

• Animals
• Anterior Chamber (immunology)
• Dermatitis, Contact (immunology)
• Fas Ligand Protein (immunology)
• Female
• Hypersensitivity, Delayed (immunology)
• Immune Tolerance
• Immunization (methods)
• Interferon-gamma (immunology)
• Lymphocyte Activation (immunology)
• Membrane Glycoproteins (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Perforin
• Pore Forming Cytotoxic Proteins (immunology)
• Serum Albumin, Bovine (administration & dosage, immunology)
• Spleen (immunology)
• T-Lymphocytes, Regulatory (immunology)