Kezuka T, Streilein J W
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts, USA.
Invest Ophthalmol Vis Sci. 2000 May;41(6):1410-21.
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.
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).
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.
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.
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。
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）。
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。
体外经TGFβ2预处理的OVA脉冲处理的APC以赋予反应性细胞在体内抑制迟发型超敏反应诱导及随后表达能力的方式激活DO11.10 T细胞。在某些方面，体外激活的DO11.10 T细胞的这些特性类似于通常在具有前房相关免疫偏离的动物脾脏中发现的传入和传出调节性T细胞的特性。
