Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany; Division of Stem Cells and Cancer, Deutsches Krebsforschungszentrum (DKFZ), and DKFZ-ZMBH Alliance, Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Evergrande Center for Immunologic Diseases, Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cell Stem Cell. 2022 May 5;29(5):760-775.e10. doi: 10.1016/j.stem.2022.04.007.
Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of blood and immune cells. Throughout life, HSPCs acquire oncogenic aberrations that can cause hematological cancers. Although molecular programs maintaining stem cell integrity have been identified, safety mechanisms eliminating malignant HSPCs from the stem cell pool remain poorly characterized. Here, we show that HSPCs constitutively present antigens via major histocompatibility complex class II. The presentation of immunogenic antigens, as occurring during malignant transformation, triggers bidirectional interactions between HSPCs and antigen-specific CD4 T cells, causing stem cell proliferation, differentiation, and specific exhaustion of aberrant HSPCs. This immunosurveillance mechanism effectively eliminates transformed HSPCs from the hematopoietic system, thereby preventing leukemia onset. Together, our data reveal a bidirectional interaction between HSPCs and CD4 T cells, demonstrating that HSPCs are not only passive receivers of immunological signals but also actively engage in adaptive immune responses to safeguard the integrity of the stem cell pool.
造血干细胞和祖细胞（HSPCs）负责产生血液和免疫细胞。在整个生命过程中，HSPCs 会获得致癌异常，从而导致血液系统癌症。尽管已经确定了维持干细胞完整性的分子程序，但仍不清楚消除干细胞池中的恶性 HSPC 的安全机制。在这里，我们表明 HSPCs 通过主要组织相容性复合体 II 持续呈现抗原。免疫原性抗原的呈递，如在恶性转化过程中发生的那样，触发 HSPC 和抗原特异性 CD4 T 细胞之间的双向相互作用，导致干细胞增殖、分化和异常 HSPC 的特异性耗竭。这种免疫监视机制有效地将转化的 HSPC 从造血系统中清除，从而防止白血病的发生。总之，我们的数据揭示了 HSPC 和 CD4 T 细胞之间的双向相互作用，表明 HSPC 不仅是免疫信号的被动接受者，而且还积极参与适应性免疫反应，以维护干细胞池的完整性。
