In vivo persistence of CD8 polarized T cell subsets producing type 1 or type 2 cytokines.
In vivo persistence of CD8 polarized T cell subsets producing type 1 or type 2 cytokines.
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DOI：
10.4049/jimmunol.161.1.97
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发表时间：
1998-07
影响因子：
4.4
通讯作者：
A. Cerwenka;Laura Carter;J. Reome;S. Swain;R. Dutton
中科院分区：
文献类型：
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作者：
A. Cerwenka;Laura Carter;J. Reome;S. Swain;R. Dutton
初始CD 8 T细胞可以极化为效应子，分别产生1型细胞因子IFN-γ和IL-2或2型细胞因子IL-4、IL-5和IL-10。为了研究效应子的极化细胞因子表型是否稳定，我们从克隆-4 TCR转基因小鼠中产生了高度细胞毒性的血凝素（HA）肽特异性CD 8 Tc 1和Tc 2（产生1型或2型细胞因子的细胞毒性CD 8 T细胞）效应子，这些效应子过继转移到同基因的成年胸腺切除的辐射和骨髓重建受体中。高度活化的原始细胞大小、CD 25 + Tc 1和Tc 2效应子产生同质的静息CD 25-CD 44（高）Ly 6C（高）Ag特异性群体，其在过继转移后持续至少13周。这些记忆性CD 8 T细胞在转移Tc 1或Tc 2效应物后13周恢复，仍然产生1型或2型细胞因子，即，IFN-γ，或IL-4和IL-5，但不存在Ag。在Tc 1和Tc 2记忆细胞群的上清液中检测到的IL-2的量与记忆CD 4细胞中的IL-2的量相当，并且Tc 1和Tc 2记忆细胞在再刺激后变得具有细胞毒性。因此，酪氨酸极化的CD 8记忆T细胞是多种细胞因子的来源，这些细胞因子被经典地认为是辅助细胞因子，这为它们在免疫应答中作为调节细胞的功能开辟了新的视角。
Naive CD8 T cells can be polarized into effectors producing the type 1 cytokines IFN-gamma and IL-2 or the type 2 cytokines IL-4, IL-5, and IL-10, respectively. To study whether the polarized cytokine phenotype of the effectors is stable, we generated highly cytotoxic hemagglutinin (HA) peptide-specific CD8 Tc1 and Tc2 (cytotoxic CD8 T cells producing type 1 or type 2 cytokines) effectors from Clone-4 TCR-transgenic mice, which were adoptively transferred into syngeneic adult thymectomized irradiated and bone marrow-reconstituted recipients. The highly activated blast-size, CD25+ Tc1 and Tc2 effectors gave rise to homogeneous resting CD25- CD44(high) Ly6C(high) Ag-specific populations, which persisted for at least 13 wk after adoptive transfer. These memory CD8 T cells, recovered 13 wk after transfer of Tc1 or Tc2 effectors, still produced either the type 1 or type 2 cytokines, i.e., IFN-gamma, or IL-4 and IL-5, respectively, upon restimulation with APCs loaded with the HA peptide, but not in the absence of Ag. The amounts of IL-2 detected in the supernatants of Tc1 and Tc2 memory populations were comparable to that in memory CD4 cells, and both Tc1 and Tc2 memory cells became cytotoxic upon restimulation. Thus, cytokine-polarized CD8 memory T cells are a source of a variety of cytokines, which were classically considered helper cytokines, opening new perspectives on their function as regulatory cells in an immune response.