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 (HSPC) 负责产生血液和免疫细胞。在整个生命过程中，HSPC 会出现可导致血液系统癌症的致癌畸变。尽管已经确定了维持干细胞完整性的分子程序，但从干细胞库中消除恶性 HSPC 的安全机制的特征仍然很差。在这里，我们显示 HSPC 通过主要组织相容性复合物 II 类组成型呈递抗原。免疫原性抗原的呈递，如发生在恶性转化过程中，会触发 HSPC 与抗原特异性 CD4 ^{+之间的双向相互作用}T 细胞，导致异常 HSPC 的干细胞增殖、分化和特异性耗竭。这种免疫监视机制有效地从造血系统中清除转化的 HSPC，从而预防白血病的发生。^{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保护干细胞库的完整性。