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 language | English |
|---|---|
| Journal | Kobe Journal of Medical Sciences |
| Volume | 59 |
| Issue number | 2 |
| Publication status | Published - Apr 25 2013 |
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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 journal › Article
}
TY - JOUR
T1 - Expansion of PD-1-positive effector CD4 T cells in an experimental model of SLE
T2 - Contribution to the self-organized criticality theory
AU - Miyazaki, Yumi
AU - Tsumiyama, Ken
AU - Yamane, Takashi
AU - Ito, Mitsuhiro
AU - Shiozawa, Shunichi
PY - 2013/4/25
Y1 - 2013/4/25
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84876436427&partnerID=8YFLogxK
M3 - Article
C2 - 23756664
AN - SCOPUS:84876436427
VL - 59
JO - Kobe Journal of Medical Sciences
JF - Kobe Journal of Medical Sciences
SN - 0023-2513
IS - 2
ER -