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The contribution of cross-presenting XCR1+ dendritic cells (DCs) and SIRPα+ DCs in maintaining T cell function during exhaustion and immunotherapeutic interventions of chronic infections remains poorly characterized. Using the mouse model of chronic LCMV infection, we found that XCR1+ DCs are more resistant to infection and highly activated compared with SIRPα+ DCs. Exploiting XCR1+ DCs via Flt3L-mediated expansion or XCR1-targeted vaccination notably reinvigorates CD8+ T cells and improves virus control. Upon PD-L1 blockade, XCR1+ DCs are not required for the proliferative burst of progenitor exhausted CD8+ T (TPEX) cells but are indispensable to sustain the functionality of exhausted CD8+ T (TEX) cells. Combining anti-PD-L1 therapy with increased frequency of XCR1+ DCs improves functionality of TPEX and TEX subsets, while increase of SIRPα+ DCs dampened their proliferation. Together, this demonstrates that XCR1+ DCs are crucial for the success of checkpoint inhibitor-based therapies through differential activation of exhausted CD8+ T cell subsets. This work was supported by grants from the Spanish Ministry of Science and Innovation (grant No. PID2019-106323RB-I00 AEI//10.13039/501100011033), the “Unidad de Excelencia María de Maeztu” funded by the MCIN and the AEI (DOI: 10.13039/501100011033; Ref: CEX2018-000792-M), “la Caixa” Foundation (HR17-00199), the Russian Science Foundation (grant No. 18-11-00171), and the Research Council of Norway (grant No. 250884).