Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ
Interleukin-10 promotes the maintenance of antitumor CD8+ T-cell effector function in situ
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DOI：
10.1182/blood.v98.7.2143
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发表时间：
2001-10-01
期刊：
影响因子：
20.3
通讯作者：
Lotze, MT
中科院分区：
文献类型：
--
作者：
Fujii, S;Shimizu, K;Lotze, MT
白细胞介素-10（IL-10）是一种多功能的细胞因子，可以对T细胞发挥抑制和刺激作用。研究了IL-10在疫苗接种后是否可以在体内作为特异性CD 8（+）细胞毒性T细胞（CTL）的免疫刺激剂，如果可以，在什么条件下。在肿瘤预防模型中，在肽脉冲的初级树突状细胞免疫之前或之后不久施用IL-10导致免疫抑制和增强肿瘤进展。然而，在加强疫苗后立即注射IL-10显著增强了抗肿瘤免疫和疫苗效力。IL-10处理3周后，对这些动物的脾细胞进行分析，结果显示CD 8（+）CD 44（hi）CD 122（+）T细胞数量增加，体外抗原特异性增殖增强。尽管细胞毒性试验不支持不同治疗组之间的差异，但在单细胞水平测量抗原特异性干扰素-γ产生的2种更灵敏的试验证明疫苗/IL-10治疗组动物中抗原特异性应答T细胞数量增加。因此，IL-10可以维持抗肿瘤CD 8（+）T细胞的数量。在过继转移研究中，IL-10维持CTL功能的能力可通过去除CD 4（+）T细胞而增强。这表明IL-10介导对CD 4（+）和CD 8（+）T细胞的对比效应，分别导致原位免疫抑制或免疫增强。对IL-10免疫生物学中这种二分法的理解可能允许设计更有效的癌症疫苗，其设计用于原位激活和维持特异性CD 8（+）T细胞效应器功能。(C)2001年，美国血液学会。
Interleukin-10 (IL-10) is a multifunctional cytokine that can exert suppressive and stimulatory effects on T cells. It was investigated whether IL-10 could serve as an immunostimulant for specific CD8(+) cytotoxic T cell (CTL) in vivo after vaccination and, if so, under what conditions. In tumor prevention models, administration of IL-10 before, or soon after, peptide-pulsed primary dendritic cell immunization resulted in immune suppression and enhanced tumor progression. Injection of IL-10, however, just after a booster vaccine significantly enhanced antitumor immunity and vaccine efficacy. Analysis of spleen cells derived from these latter animals 3 weeks after IL-10 treatment revealed that the number of CD8(+) CD44(hi) CD122(+) T cells had increased and that antigen-specific proliferation in vitro was enhanced. Although cytotoxicity assays did not support differences between the various treatment groups, 2 more sensitive assays measuring antigen-specific interferon-gamma production at the single-cell level demonstrated increases in the number of anti gen-spec ific responder T cells in animals in the vaccine/IL-10 treatment group. Thus, IL-10 may maintain the number of antitumor CD8(+) T cells. In adoptive transfer studies, the ability of IL-10 to maintain CTL function could be enhanced by the depletion of CD4(+) T cells. This suggests that IL-10 mediates contrasting effects on both CD4(+) and CD8(+) T cells that result in either immune dampening or immune potentiation in situ, respectively. Appreciation of this dichotomy in IL-10 immunobiology may allow for the design of more effective cancer vaccines designed to activate and maintain specific CD8(+) T-cell effector function in situ. (C) 2001 by The American Society of Hematology.