The suppression of delayed-type hypersensitivity by CD8+ regulatory T cells requires interferon-gamma.
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.
Cone
Robert E
RE
Department of Immunology, The University of Connecticut Health Center, Farmington, CT 06030-3105, USA. Cone@UCHC.EDU
Li
Xingya
X
Sharafieh
Roshanak
R
O'Rourke
James
J
Vella
Anthony T
AT
D000818:Animals; D000867:Anterior Chamber / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007108:Immune Tolerance; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C038601:trinitrophenyl-bovine serum albumin; D054353:Perforin; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma