急性髓细胞白血病（AML）是常见的造血系统疾病之一。由于疾病或治疗相关性血小板减少的高发率，AML需要进行多次血小板输输治疗，这可能会引发针对血小板的体液免疫反应。一些AML患者在多次输血后会发展出抗HLA免疫反应。因此，我们假设不同的免疫活化状态可能与抗HLA异基因免疫化状态相关。我们通过流式细胞术和单细胞多组学分析，测试了这一假设。比较抗HLA异基因免疫化和非免疫化AML患者的免疫状态，发现CD4+ T淋巴细胞（TL）亚群及其免疫调控分子的表型和功能存在差异。免疫化患者的CD4+ TL表现出免疫活化特征，CD40和OX40水平较健康供体细胞高。然而，非免疫化患者的差异更为显著。这些患者的CD40和OX40水平较免疫化患者低，而PD1水平较高。此外，非免疫化患者的调节性T细胞（Treg）比例更大且更具功能性。这些结果得到了对传统CD4+ TL、Tfh循环细胞和Treg免疫反应分子的多组学分析支持。因此，我们的结果揭示了在输血AML患者中，与抗HLA异基因免疫化状态相关的CD4+ TL特征的差异性。这些差异在特定抗原无关的情况下刻画了CD4+ TL，应在考虑患者对感染、疫苗接种或移植的免疫反应时予以考虑。版权所有 © 2023 Khelfa, Leclerc, Kerbrat, Boudjemai, Benchouaia, Neyrinck-Leglantier, Cagnet, Berradhia, Tamagne, Croisille, Pirenne, Maury and Vingert.

Acute myeloid leukemia (AML) is one of the commonest hematologic disorders. Due to the high frequency of disease- or treatment-related thrombocytopenia, AML requires treatment with multiple platelet transfusions, which can trigger a humoral response directed against platelets. Some, but not all, AML patients develop an anti-HLA immune response after multiple transfusions. We therefore hypothesized that different immune activation profiles might be associated with anti-HLA alloimmunization status.We tested this hypothesis, by analyzing CD4+ T lymphocyte (TL) subsets and their immune control molecules in flow cytometry and single-cell multi-omics.A comparison of immunological status between anti-HLA alloimmunized and non-alloimmunized AML patients identified differences in the phenotype and function of CD4+ TLs. CD4+ TLs from alloimmunized patients displayed features of immune activation, with higher levels of CD40 and OX40 than the cells of healthy donors. However, the most notable differences were observed in non-alloimmunized patients. These patients had lower levels of CD40 and OX40 than alloimmunized patients and higher levels of PD1. Moreover, the Treg compartment of non-alloimmunized patients was larger and more functional than that in alloimmunized patients. These results were supported by a multi-omics analysis of immune response molecules in conventional CD4+ TLs, Tfh circulating cells, and Tregs.Our results thus reveal divergent CD4+ TL characteristics correlated with anti-HLA alloimmunization status in transfused AML patients. These differences, characterizing CD4+ TLs independently of any specific antigen, should be taken into account when considering the immune responses of patients to infections, vaccinations, or transplantations.Copyright © 2023 Khelfa, Leclerc, Kerbrat, Boudjemai, Benchouaia, Neyrinck-Leglantier, Cagnet, Berradhia, Tamagne, Croisille, Pirenne, Maury and Vingert.