Lysis of keratinocytes by IL-2-activated peripheral blood lymphocytes.
Lysis of keratinocytes by IL-2-activated peripheral blood lymphocytes.
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IL-2 激活的外周血淋巴细胞裂解角质形成细胞。
DOI：
10.1111/1523-1747.ep12515933
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Santos,EB
中科院分区：
文献类型：
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作者：
Symington,FW;Santos,EB
白细胞介素2(IL-2)激活的外周血单核细胞(PBMC)在体外可杀伤肿瘤细胞，但基本上不杀伤正常细胞。本文报道了JL-2诱导的体外裂解正常人角质形成细胞(KC)的抗角质形成细胞(抗KG)细胞毒效应。通过在不同浓度的重组IL-2中培养PBMC 1-8d产生效应器，然后针对51Cr标记的靶点进行检测。用103U/mI的IL-2刺激效应细胞8d后，在无血清条件下培养的自体或同种异体KC容易裂解贴壁或胰酶消化。IL-2诱导的抗KG效应呈剂量依赖关系，低浓度IL-2作用24 h后抗KC活性增强。尽管在IL-2中过夜培养后抗KG活性增加，但以每106个效应细胞的裂解单位(LU)计的最大效应效力需要4d的IL-2处理。以每输入PBMC的LU计的最大效应量出现在IL-2治疗8d后。抗体加补体耗竭研究表明，抗KC效应者主要具有CD16-/CD3-/CD2+表型。在冷靶向竞争实验中，未标记的K562细胞完全抑制了51Gr-KC的裂解；干扰素-g处理(2.5U/mI-500U/rn1重组干扰素-g 48-72小时)降低了KG对这些效应器的裂解敏感性。因此，IL-2处理的PBMC诱导非T细胞，自然杀伤样效应物，可以同时溶解自体和同种异体KG。此外，KG与其他类型的细胞相似，这些细胞在干扰素-g治疗后对非MHG限制性裂解产生抵抗力。最后，与特异性T细胞裂解相比，干扰素-g处理对这些效应物裂解KG的效果的对比表明，在体内的表皮免疫应答中，干扰素-g可以促进非MHG限制性裂解向MHC限制性裂解的转变。
Interleukin 2 (IL-2) – activated peripheral blood mononuclear cells (PBMC) have been reported to lyse tumor cells while essentially sparing normal cells in vitro. This report concerns JL-2 – induced anti-keratinocyte (anti-KG) cytotoxic effectors that lyse normal human keratinocytes (KC) in vitro. Effectors were generated by culturing PBMC for 1–8 d in various concentrations of recombinant IL.-2 and then assayed against51Cr-labeled targets. Effectors stimulated with 103U/mi of IL-2 for 8 d readily lysed adherent or trypsinized autologous or allogeneic KC cultured in serum- free medium. Induction of anti-KG effectors was IL-2 dose- dependent, with as little as 12–25 U/ml of IL-2 inducing increased anti-KC activity after 24 h of treatment. Although anti-KG activity was increased after overnight culture in IL-2, maximal effector potency in terms of lytic units (LU) per 106effector cells required 4 d of IL-2 treatment. Maximal effector yield in terms of LU per input PBMC occurred after 8 d of IL-2 treatment. Antibody plus complement depletion studies showed that the anti-KC effectors predominantly have a CD16—/CD3—/CD2 + phenotype. A natural killer (NK)-like specificity of the effectors was suggested by two findings: unlabeled K562 cells totally inhibited lysis of51Gr- KC in cold target competition assays, and interferon gamma (IFN-g) treatment (2.5 U/mI -500 U/rn1 of recombinant IFN-g for 48–72 h) down-regulated KG susceptibility to lysis by these effectors. Thus, IL-2 treatment of PBMC induces non-T cell, natural killer-like effectors that can lyse both autologous and allogeneic KG. Furthermore, KG resemble other cell types that become resistant to non-MHG- restricted lysis after treatment with IFN-g. Finally, the contrasting effects of IFN-g treatment on KG lysis by these effectors, as opposed to lysis by specific T cells, suggests that IFN-g could promote a shift from non-MHG-restricted to MHC-restricted KG lysis during epidermal immune sponses in vivo.