title: Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE: contribution to the self-organized criticality theory.
abstract: We have developed a systems biology concept to explain the origin of systemic autoimmunity. From our studies of systemic lupus erythematosus (SLE) we have concluded that this disease is the inevitable consequence of over-stimulating the host's immune system by repeated exposure to antigen to levels that surpass a critical threshold, which we term the system's "self-organized criticality". We observed that overstimulation of CD4 T cells in mice led to the development of autoantibody-inducing CD4 T cells (aiCD4 T) capable of generating various autoantibodies and pathological lesions identical to those observed in SLE. We show here that this is accompanied by the significant expansion of a novel population of effector T cells characterized by expression of programmed death-1 (PD-1)-positive, CD27(low), CD127(low), CCR7(low) and CD44(high)CD62L(low) markers, as well as increased production of IL-2 and IL-6. In addition, repeated immunization caused the expansion of CD8 T cells into fully-matured cytotoxic T lymphocytes (CTL) that express Ly6C(high)CD122(high) effector and memory markers. Thus, overstimulation with antigen leads to the expansion of a novel effector CD4 T cell population that expresses an unusual memory marker, PD-1, and that may contribute to the pathogenesis of SLE.
authors.affiliation: Department of Medicine, Kyushu University Beppu Hospital, Beppu, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Ken
authors.initials: K
authors.lastname: Tsumiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamane
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ito
authors.forename: Shunichi
authors.initials: S
authors.lastname: Shiozawa
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D019041:L-Selectin / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis* / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019041:L-Selectin