CD8(+) regulatory T cells limit immunopathology but impair viral clearance in Hantaan virus infection.

HLA-E/Qa-1-restricted CD8+ regulatory T cells are reduced and terminally differentiated in HFRS patients, and their Qa-1 interaction in mice restrains renal immunopathology.

• Why it matters: Viral hemorrhagic fever involves a tradeoff where CD8+ T cells clear Hantaan virus but also drive damaging immunopathology; the role of Qa-1/HLA-E-restricted CD8+ Tregs was unclear.
• What they did: The authors profiled a CD122+ Eomes+ CD49d lo KIR+ CD8+ Treg subset in HFRS patients and in a murine HTNV infection model, identified Qa-1-binding HTNV nonapeptides, and tested WT versus D227K knock-in mice after peptide immunization and challenge.
• The result: WT mice showed attenuated renal immunopathology, while D227K mice had enhanced viral clearance in spleen and kidney but exacerbated renal immunopathology; Qa-1-restricted Tregs suppressed effector proliferation via TGF-β, and D227K reshaped Treg function.

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