Daan Pieren

140 Chapter 5 coughing ( Figure 6L ), which may suggest delayed viral clearance. However, the frequency of activated KIR + RA + T cells did not correlate with the duration of fever ( Figure 6M ) or the other symptoms assessed separately (data not shown). Taken together, these data establish a potential clinical relevance of KIR + RA + T cells as immunoregulatory cells that may negatively affect the resolution of infection and may prolong influenza A-induced symptoms in older adults. 0 10 20 30 40 0 20 40 60 80 Symptom score % CD69 + of KIR + RA + T cells 0 5 10 15 0 20 40 60 80 Fever (days) % CD69 + of KIR + RA + T cells r = -0.120 p = 0.67 0 20 40 60 80 0 20 40 60 80 Cough (days) % CD69 + of KIR + RA + T cells r = 0.573 p = 0.03 r = 0.604 p = 0.02 K L M C A B 0 +2 +8 Healthy 0 20 40 60 80 %CD69 + of KIR + RA + T cells *** *** *** ns ns Time after fever onset (weeks) 0 +2 +8 Healthy 0 10 20 30 40 50 % KIR + RA + within CD8 + T cells Time after fever onset (weeks) * * ns ns ns Influenza A Influenza A Influenza A D Seasonal coronavirus 0 +2 +8 Healthy 0 5 10 15 %CD69 + of KIR + RA + T cells * * ** ns ns Time after fever onset (weeks) hMPV Influenza B Rhinovirus E 0 +2 +8 Healthy 0 20 40 60 80 %CD69 + of KIR + RA + T cells ns Time after fever onset (weeks) 0.17 0.15 0.0947 ns 0 +2 +8 Healthy 0 5 10 15 20 %CD69 + of KIR + RA + T cells ns ns ns ns ns Time after fever onset (weeks) 0 +2 +8 Healthy 0 10 20 30 40 %CD69 + of KIR + RA + T cells * ns ns 0.12 0.14 Time after fever onset (weeks) F G I 0 50 100 150 200 Time after fever onset (weeks) Influenza-specific (GILGFVFTL + ) cells within subset (#) T NAIVE T EMRA NKG2A + RA + KIR + RA + T CM T EM 0 +2 +8 0 +2 +8 0 +2 +8 0 +2 +8 0 +2 +8 0 +2 +8 SARS-CoV-2 J 0 +2 +4 Healthy 0 5 10 15 20 %CD69 + of KIR + RA + T cells * ** ** ns ns Time after fever onset (weeks) RSV 0 +2 +8 Healthy 0 20 40 60 %CD69 + of KIR + RA + T cells Time after fever onset (weeks) H T NAIVE T CM T EM T EMRA KIR + RA + NKG2A + RA + 0 20 40 60 80 %CD69 + of subset ** ** ** ** ** Figure 6. KIR + RA + T cells are highly activated during acute respiratory infection in older adults as bystander cells and correlate with prolonged disease.