Induction of CD4^+ Regulatory T Cells by TPA in Mice : Contra-suppression by CD8^+T Cells
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概要
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Among the eight inbred mouse strains employed in our preceding report, 12-O-tetradecanoylphorbol 13-ac-etate(TPA)painting alone induced CD4^+ regulatory T(Tr)cells in four strains(e.g., C3H/He)at 6-8 weeks of age, but not in the remaining strains(e.g., C57BL/6, BALB/c). In the present study, the effect of growth from 4-14weeks on delayed-type hypersensitivity(DTH)response was investigated in three inbred murine strains, C3H/He(H-2k), C57BL/6(H-2b)and BALB/c(H-2d)mice. In all strains older than 10 weeks, DTH response was suppressed exclusively by TPA painting. The defect of suppressive activity for DTH in several of the strains at 6-8 weeks of age was dependent on the presence of cells, which blocked regulatory cell activity at 6-8 weeks of age, but not at 10 weeks of age. The age-dependent difference in regulatory activity was caused by the presence of CD8^+ contra-regulatory T(Tcr)cells. CD8^+ contra-regulatory T cells are required to contact regulatory cells in order to block DTH suppressive activity. Adhesion molecules were of great importance in contra-suppression, as antibody treatment to LFA-1 or ICAM-1 blocked this activity. ICAM-1 expression on CD4 T cells greatly increased following growth in 10 week-BALB/c mice receiving TPA than 6-week-old mice, however, a slight increase in growth occurred in 6-to-10-week-old animals in which TPA was absent. The degree of increment in body weight was very similar in these inbred strains. Thymus involution in C3H/He mice was the earliest signal among these mice. This result may suggest that the period of differentiation and maturation of T cells in a first lymphoid tissue for the growth process differs in these three inbred strains. This study provides an interesting example of genetic control of maturation or proliferation of peripheral T cells.
- 公益社団法人日本薬学会の論文
- 2002-02-01
著者
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Negoro Takaharu
Department of Phamacogenomics School of Phamaceutical Sciences Showa University
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WATANABE Mitsuo
Department of Neurosurgery, Koyanagi Memorial Hospital
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Satoh Kazue
Department of Anatomy, School of Medicine,Showa University
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TOBE Takashi
Department of Physiological Chemistry, School of Pharmaceutical Sciences Showa University
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Satoh Kazue
Department Of Medicinal Information School Of Pharmaceutical Sciences
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Watanabe Mitsuo
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Teikyo University
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Tobe T
Showa Univ. Tokyo Jpn
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Tobe Takashi
Department Of Biochemistry School Of Medicine Showa University
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IINUMA Fumio
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University
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Satoh Kazue
Department Of Anatomy School Of Medicine
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Iinuma Fumio
Department Of Analytical Chemistry Faculty Of Pharmaceutical Sciences Teikyo University
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Negoro Takaharu
Department Of Biochemistry School Of Medicine Showa University
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Negoro Takaharu
Department of Medicinal Information, School of Pharmaceutical Sciences
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WATANABE Mitsuo
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Teikyo University
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