1998 Fiscal Year Final Research Report Summary
Abnormalities of T lymphocyte subsets in systemic sclerosis and analyses of the inducing cytokines
| Project/Area Number |
09670891
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| Research Category |
Grant-in-Aid for Scientific Research (C).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Yokohama City University |
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Principal Investigator |
SASAKI Tetsuo Yokohama City University, School of Medicine, Dermatology, Assistant Professor, 医学部附属病院, 講師 (10170680)
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| Project Period (FY) |
1997 – 1998
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| Keywords | systemic sclerosis / T lymphocyte subsets / cytokine / tight-skin mouse / flow cytometry / interleukin 12 / interleukin 4 / antinuclear antibody |
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| Research Abstract |
We examined the frequencies of interleukin (IL)-4 or IL-2 producing CD4^+ or CD8^+T cells in peripheral blood mononuclear cells (PBMC_5) from patients with systemic sclerosis (SSc). The frequency of CD4^+T cells was negatively correlated with duration of SSc, whereas the frequency of CD8^+T cells was not correlated with duration. The frequencies of IL-4 producing (IL-4^+) cells in CD4^+T cells and in CD8^+T cells from the patients with SSc were both significantly higher than those from the healthy controls. In contrast, the frequencies of IL-2 producing (IL-2^+) cells in CD4^+T cells and in CD8^+T cells from patients with SSc were both significantly lower than that from the healthy controls. Further, the ratios of IL-4^+/IL-4^+ + IL-2^+ in CD4^+T cells and in CD8^+T cells were both negatively correlated with the disease duration of SSc. These results suggest that type 2 cytokine-producing T cells, not only CD4^+T cells but also CD8^+T cells, have important roles in the pathogenesis of
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SSc, especially in the early phase of SSc. We then examined the effect of IL-12 encoding plasmid (pCAGGSIL-12) on the disease progression of Tsk/+ mice. pCAGGSIL-12 plasmid or pCAGGS parental vector was injected intramuscularly 7 times with 3 weeks intervals into Tsk/+ mice. One week after the last injection, pCAGGSIL-12 administered Tsk/+ mice exhibited a marked decrease in the skin thickness compared with the mice treated with pCAGGS vector. The serum levels of antinuclear antibodies were diminished in pCAGGSIL-12 treated mice. IL-4 production by spleen cells from pCAGGSIL-12 plasmid treated mice was significantly lower than that from vector treated mice. These results indicate that pCAGGSIL-12 administration into Tsk/+ mice had beneficial effects in preventing the collagen accumulation in the skin and suppressing the autoimmunity via improvement of Th1/Th2 balance. The present study suggests that the IL-12 encoding plasmid administration might have a therapeutic effect on systemic sclerosis. Less
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