Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE: Contribution to the self-organized criticality theory

Yumi Miyazaki, Ken Tsumiyama, Takashi Yamane, Mitsuhiro Ito, Shunichi Shiozawa

Research output: Contribution to journalArticle

4 Citations (Scopus)

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, CD27low, CD127low, CCR7low and CD44highCD62Llow 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 Ly6ChighCD122high 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.

Original languageEnglish
JournalKobe Journal of Medical Sciences
Volume59
Issue number2
Publication statusPublished - Apr 25 2013

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Systemic Lupus Erythematosus
Theoretical Models
T-Lymphocytes
Autoantibodies
Antigens
Systems Biology
Cytotoxic T-Lymphocytes
Autoimmunity
Population
Interleukin-2
Immune System
Immunization
Interleukin-6

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE : Contribution to the self-organized criticality theory. / Miyazaki, Yumi; Tsumiyama, Ken; Yamane, Takashi; Ito, Mitsuhiro; Shiozawa, Shunichi.

In: Kobe Journal of Medical Sciences, Vol. 59, No. 2, 25.04.2013.

Research output: Contribution to journalArticle

Miyazaki, Yumi ; Tsumiyama, Ken ; Yamane, Takashi ; Ito, Mitsuhiro ; Shiozawa, Shunichi. / Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE : Contribution to the self-organized criticality theory. In: Kobe Journal of Medical Sciences. 2013 ; Vol. 59, No. 2.
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