对经转化生长因子β2处理的抗原呈递细胞体外激活的T细胞的体内调节特性分析。

Analysis of in vivo regulatory properties of T cells activated in vitro by TGFbeta2-treated antigen presenting cells.

作者信息

Kezuka T, Streilein J W

机构信息

Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.

出版信息

Invest Ophthalmol Vis Sci. 2000 May;41(6):1410-21.

PMID:10798657

Abstract

PURPOSE

To determine whether naive T cells activated in vitro by antigen-pulsed, transforming growth factor(beta) (TGFbeta)-treated antigen presenting cells (APCs) acquire the capacity to suppress the induction and expression of delayed hypersensitivity in vivo.

METHODS

Naive ovalbumin (OVA)specific T cells from DO 11.10 Tcr transgenic mice were stimulated in vitro with OVA-pulsed TGF(beta2)-treated APCs. The cultured cells were harvested and assayed for in vitro production of mature TGFbeta. Similar cells were coinjected with primed OVA-specific BALB/c T cells plus OVA-pulsed APCs into ear pinnae of normal BALB/c mice (assay for delayed hypersensitivity expression) or coinjected with OVA-pulsed APCs into footpads of naive DO11.10 mice whose draining lymph node cells were harvested 4 days later and assayed in vitro for capacity to secrete interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) when stimulated with OVA (assay for induction of delayed hypersensitivity).

RESULTS

DO11.10 T cells activated in vitro by OVA-pulsed TGFbeta2-treated APCs secreted large amounts of mature TGFbeta and suppressed the expression of delayed hypersensitivity in a local adoptive transfer assay. Suppression was reversed in the presence of neutralizing anti-TGFbeta antibodies. In addition, in vitro generated regulatory T cells influenced naive T cells in DO11.10 mice that were responding to an initial immunization with OVA to secrete IL-4, rather than IFN-gamma. This influence was independent of TGFbeta.

CONCLUSIONS

OVA-pulsed APCs, pretreated in vitro with TGF(beta)2, activate DO11.10 T cells in a manner that endows the responding cells with the capacity to suppress the induction and then the expression of delayed hypersensitivity in vivo. In certain ways, these properties of in vitro-activated DO11.10 T cells resemble the properties of afferent and efferent regulatory T cells typically found in the spleens of animals with anterior chamber-associated immune deviation.

摘要

目的

确定经抗原脉冲处理、转化生长因子β（TGFβ）处理的抗原呈递细胞（APC）在体外激活的初始T细胞是否获得在体内抑制迟发型超敏反应诱导和表达的能力。

方法

用OVA脉冲处理、TGFβ2处理的APC在体外刺激来自DO11.10 Tcr转基因小鼠的初始卵清蛋白（OVA）特异性T细胞。收获培养的细胞并检测其体外成熟TGFβ的产生。将类似的细胞与致敏的OVA特异性BALB/c T细胞加OVA脉冲处理的APC共同注射到正常BALB/c小鼠的耳廓中（检测迟发型超敏反应表达），或将其与OVA脉冲处理的APC共同注射到初始DO11.10小鼠的足垫中，4天后收集其引流淋巴结细胞，并在体外检测用OVA刺激时分泌干扰素γ（IFN-γ）和白细胞介素-4（IL-4）的能力（检测迟发型超敏反应诱导）。

结果

经OVA脉冲处理、TGFβ2处理的APC在体外激活的DO11.10 T细胞分泌大量成熟TGFβ，并在局部过继转移试验中抑制迟发型超敏反应的表达。在存在中和性抗TGFβ抗体的情况下，抑制作用被逆转。此外，体外产生的调节性T细胞影响DO11.10小鼠中对OVA初次免疫有反应的初始T细胞分泌IL-4，而不是IFN-γ。这种影响与TGFβ无关。