Purpose

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome mainly caused by uncontrolled activation of antigen presenting cells and CD8 T cells. CD8 T cell exhaustion is a known phenomenon in chronic viral infections and cancer. However, the role of T cell exhaustion is not yet identified in HLH in the background of persistent inflammation. So, currently, we have characterized the CD8 T cells using flow cytometry to understand the phenomenon of exhaustion in these cells in HLH.

Methods

We have comprehensively evaluated lymphocyte subsets and characterized CD8 T cells using immunophenotypic markers like PD1, TIM3, LAG3, Ki67, Granzyme B, etc. in a cohort of 21 HLH patients. Effector cytokine secretion and degranulation by CD8 T cells are also studied.

Results

Our findings indicate skewed lymphocyte subsets and aberrantly activated CD8 T cells in HLH. CD8 T cells exhibit significantly increased expression of PD1, TIM3, and LAG3 prominently in primary HLH as compared to controls. PD1 + CD8 T cells express elevated levels of Granzyme B and Ki67. Moreover, CD8 T cells are hypofunctional as evidenced by significantly reduced cytokine secretion and compromised CD107a degranulation.

Conclusion

The study has revealed that CD8 + cytotoxic T lymphocytes from HLH patients exhibited high expression of exhaustion markers with overall impaired function. To the best of our understanding, this is the first report suggesting functional exhaustion of CD8 T cells in both primary and secondary HLH. Future studies to understand the association of exhaustion with disease outcome are needed for its probable therapeutic implementation.

中文翻译：

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CD8 + T 细胞在噬血细胞性淋巴组织细胞增多症中表现出疲惫的表型

目的

噬血细胞性淋巴组织细胞增多症 (HLH) 是一种高炎症综合征，主要由抗原呈递细胞和 CD8 T 细胞的失控激活引起。CD8 T 细胞衰竭是慢性病毒感染和癌症中的一种已知现象。然而，在持续炎症的背景下，T 细胞耗竭在 HLH 中的作用尚未确定。因此，目前，我们使用流式细胞术对 CD8 T 细胞进行了表征，以了解 HLH 中这些细胞的衰竭现象。

方法

我们在一组 21 名 HLH 患者中使用免疫表型标志物（如 PD1、TIM3、LAG3、Ki67、颗粒酶 B 等）全面评估了淋巴细胞亚群并表征了 CD8 T 细胞。还研究了 CD8 T 细胞的效应细胞因子分泌和脱粒。

结果

我们的研究结果表明 HLH 中的淋巴细胞亚群偏斜和异常激活的 CD8 T 细胞。与对照组相比，CD8 T 细胞在原发性 HLH 中表现出显着增加的 PD1、TIM3 和 LAG3 表达。PD1 + CD8 T 细胞表达水平升高的颗粒酶 B 和 Ki67。此外，CD8 T 细胞功能减退，细胞因子分泌显着减少和 CD107a 脱粒受损就证明了这一点。

结论

该研究表明，来自 HLH 患者的 CD8 + 细胞毒性 T 淋巴细胞表现出高表达的衰竭标志物，总体功能受损。据我们所知，这是第一份表明 CD8 T 细胞在原发性和继发性 HLH 中功能衰竭的报告。未来的研究需要了解疲惫与疾病结果之间的关系，以实现其可能的治疗实施。