Vitallé Joana, Bachiller Sara, Dominguez-Molina Beatriz, Moysi Eirini, Ferrando-Martínez Sara, Camacho-Sojo María Inés, Gallego Isabel, Pérez-Gómez Alberto, Jiménez-Leon María Reyes, Gasca-Capote Carmen, Ostos Francisco José, Rafii-El-Idrissi Benhnia Mohammed, Via Laura E, Mochón Antonio, López-Cortes Luis Fernando, Petrovas Constantinos, Koup Richard A, Ruiz-Mateos Ezequiel
Institute of Biomedicine of Seville, IBiS/Virgen Del Rocío University Hospital/CSIC/University of Seville Clinical Unit of Infectious Diseases, Microbiology and Parasitology Seville Spain.
Department of Medical Biochemistry Molecular Biology, and Immunology School of Medicine University of Seville Seville Spain.
MedComm (2020). 2025 Sep 12;6(9):e70354. doi: 10.1002/mco2.70354. eCollection 2025 Sep.
Dendritic cells (DC) are known to modulate antiviral immune responses; however, the knowledge about the role of different DC subsets in antiviral T cell priming in human tissues remains uncompleted. In the context of HIV infection, we determined the phenotype and location of plasmacytoid and CD141+ myeloid DCs (pDCs and mDCs) in lymph nodes of people living with HIV (PLWH). We found an interaction between pDCs and CD141+ mDCs with CD8+ T cells, being associated with participants' viral levels in blood and tissue. Moreover, we demonstrated a higher and more polyfunctional superantigen- and HIV-specific CD8+ T cell response after the coculture with Toll-like receptor (TLR)-primed pDCs and CD141+ mDCs. Last, we showed the potential of programmed cell death-1 (PD-1) blocking using pembrolizumab to further increase antigen-specific CD8+ T cell response along with TLR agonists. Therefore, these results showed a cooperation between pDCs, CD141+ mDCs and CD8+ T cells in lymph nodes of PLWH, which is associated with higher HIV control, highlighting the importance of DC subsets crosstalk to achieve a more potent anti-HIV response and support the use of DC-based immunotherapies for HIV control.
已知树突状细胞（DC）可调节抗病毒免疫反应；然而，关于不同DC亚群在人体组织中抗病毒T细胞启动过程中的作用，相关知识仍不完善。在HIV感染的背景下，我们确定了HIV感染者（PLWH）淋巴结中浆细胞样和CD141⁺ 髓样DC（pDC和mDC）的表型和位置。我们发现pDC与CD141⁺ mDC与CD8⁺ T细胞之间存在相互作用，这与参与者血液和组织中的病毒水平相关。此外，我们证明，与经Toll样受体（TLR）启动的pDC和CD141⁺ mDC共培养后，会产生更高且更具多功能性的超抗原特异性和HIV特异性CD8⁺ T细胞反应。最后，我们展示了使用派姆单抗阻断程序性细胞死亡蛋白1（PD-1）与TLR激动剂联合使用，进一步增强抗原特异性CD8⁺ T细胞反应的潜力。因此，这些结果表明PLWH淋巴结中的pDC、CD141⁺ mDC和CD8⁺ T细胞之间存在合作，这与更好的HIV控制相关，突出了DC亚群间相互作用对于实现更有效的抗HIV反应的重要性，并支持使用基于DC的免疫疗法来控制HIV。
