Acute lymphopenia-induced homeostatic proliferation (HP) of T cells promotes antitumor immunity, but the mechanism is unclear. We hypothesized that this is due to a lack of inhibitory signals that allows activation of T cells with low affinity for self-antigens. Tumors resist immunity in part by expressing inhibitory molecules such as PD-1 ligand 1 (PD-L1), B7-H4, and TGF-beta. In irradiated mice undergoing HP, we found that T cells displayed a severe deficit in the activation-induced expression of inhibitory molecules PD-1 and CTLA-4, and TGF-beta1-induced expression of Foxp3. HP T cells were also less suppressed by B7-H4/Ig and, unlike control T cells, failed to produce IL-10 in response to this molecule. This deficiency in regulation was reversed as normal T-cell numbers were restored. We conclude that T cells are weakly regulated by inhibitory molecules during the acute phase of HP, which could explain their increased effectiveness in cancer immunotherapy.
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机译：急性淋巴细胞减少诱导的T细胞稳态增殖（HP）促进抗肿瘤免疫，但机制尚不清楚。我们假设这是由于缺乏抑制信号而导致的，这些信号允许以对自身抗原的低亲和力激活T细胞。肿瘤通过表达抑制分子（例如PD-1配体1（PD-L1），B7-H4和TGF-beta）部分抵抗免疫力。在接受过HP照射的小鼠中，我们发现T细胞在激活诱导的抑制分子PD-1和CTLA-4的表达以及TGF-beta1诱导的Foxp3的表达中显示出严重的缺陷。 HP T细胞也较少受到B7-H4 / Ig的抑制，与对照T细胞不同，HP T细胞未能响应此分子而产生IL-10。随着正常T细胞数量的恢复，这种调节缺陷得以逆转。我们得出的结论是，在HP的急性期，T细胞受到抑制分子的弱调控，这可以解释其在癌症免疫治疗中的有效性提高。
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