Polarization of Human CD4+ T Cells to T-helper Type 1 and Type 2 Cells by Superantigen Stimulation

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  • ヒトCD4+T細胞のスーパー抗原によるTh1,Th2 type細胞への偏向

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説明

免疫応答に重要な役割をもつCD4+ヘルパーT細胞に2つのサブセット(Th1,Th2)があり, Th1/Th2バランスの変調が,様々な疾患の病因に大きく関与していることが明らかになってきた.これまで,人工的な刺激物質である抗CD3抗体などを用いてin vitro実験系で偏向させたヒトTh1細胞とTh2細胞サンプルを得るまでに4週間ほど時間が必要であった.本研究では自然環境においてヒトT細胞の強力な活性化抗原である細菌性スーパー抗原を用い,短期間にTh1細胞とTh2細胞を誘導できる実験システムを確立した.ヒトT細胞の未感作分画であるCD4^+CD45RA^+T細胞は1週間以内にTh1細胞とTh2細胞に分化を遂げた.一方,末梢血感作T細胞分画であるCD4^+CD45RO^+T細胞はTh1/Th2偏向刺激に対して抵抗性を示した.ケモカインレセプター表現の解析では,従来の報告と同様にCD4^+CD45RA^+T細胞から誘導されたTh1細胞はCXCR3陽性であり,Th2細胞はCXCR3陰性を示す成績が得られた.また,Th1/Th2偏向刺激を受けたCD4^+CD45RO^+T細胞は,いずれにおいてもCXCR3陽性細胞とCXCR3陰性細胞が混在していた.

To induce T-helper type 1 (Th1) and type 2 (Th2) cells in a short period, human adult peripheral blood T cells were cultured in combination with toxic shock syndrome toxin-1 (TSST-1) in the presence of IL-12 and anti-IL-4 antibody (Th1-polarizing condition), or in combination with IL-4, anti-IL-12 and anti-IFN-γ antibodies (Th2-polarizing condition) in the presence of IL-2 for a total of 7 days. CD4^+ T cell blasts that resulted from the Th1-polarizing condition of unprimed type CD4^+CD45RA^+ T cells exhibited massive IFN-γ production but quite low IL-4 production upon re-stimulation with TSST-1. Around 90% of the cells that exhibited the typical Th1 response were CXCR3-positive. These cells were divided into CCR4-positive and CCR4-negative fractions. The CD4^+ T cell blasts that resulted from the Th2-polarizing condition exhibited massive IL-4 production but quite low IFN-γ production. Around 70% of the cells that exhibited the typical Th2 response were CXCR3-negative but were CCR4-positive. Two preparations of CD4^+ T cell blasts resulting from the Th1 and the Th2 polarizing conditions of the memory-type CD4^+CD45RO^+ T cells produced both IFN-γ and IL-4 in substantial units and contained both CXCR3-positive and CXCR3-negative cells. The results indicated that the new system induced typical Th1 and Th2 cells from unprimed CD4^+ T cells within 7 days and that the expression of CXCR3 was the key factor to discriminate Th1 and Th2 cells.

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