tetano
Editor, Senior Moderator
Nat Commun. 2018 Feb 26;9(1):824. doi: 10.1038/s41467-018-03243-7.
[h=1]Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease.[/h] Wang Z[SUP]1,[/SUP][SUP]2[/SUP], Zhu L[SUP]1[/SUP], Nguyen THO[SUP]2[/SUP], Wan Y[SUP]1[/SUP], Sant S[SUP]2[/SUP], Qui?ones-Parra SM[SUP]2[/SUP], Crawford JC[SUP]3[/SUP], Eltahla AA[SUP]4[/SUP], Rizzetto S[SUP]4[/SUP], Bull RA[SUP]4[/SUP], Qiu C[SUP]1[/SUP], Koutsakos M[SUP]2[/SUP], Clemens EB[SUP]2[/SUP], Loh L[SUP]2[/SUP], Chen T[SUP]1[/SUP], Liu L[SUP]1[/SUP], Cao P[SUP]5[/SUP], Ren Y[SUP]1[/SUP], Kedzierski L[SUP]2[/SUP], Kotsimbos T[SUP]6[/SUP], McCaw JM[SUP]5[/SUP], La Gruta NL[SUP]2,[/SUP][SUP]7[/SUP], Turner SJ[SUP]2,[/SUP][SUP]8[/SUP], Cheng AC[SUP]9[/SUP], Luciani F[SUP]4[/SUP], Zhang X[SUP]1[/SUP], Doherty PC[SUP]2,[/SUP][SUP]3[/SUP], Thomas PG[SUP]3[/SUP], Xu J[SUP]10[/SUP], Kedzierska K[SUP]11,[/SUP][SUP]12[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8[SUP]+[/SUP] T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]PD-1[SUP]+[/SUP] CD8[SUP]+[/SUP] T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαβ clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.
PMID: 29483513 DOI: 10.1038/s41467-018-03243-7
[h=1]Clonally diverse CD38+HLA-DR+CD8+ T cells persist during fatal H7N9 disease.[/h] Wang Z[SUP]1,[/SUP][SUP]2[/SUP], Zhu L[SUP]1[/SUP], Nguyen THO[SUP]2[/SUP], Wan Y[SUP]1[/SUP], Sant S[SUP]2[/SUP], Qui?ones-Parra SM[SUP]2[/SUP], Crawford JC[SUP]3[/SUP], Eltahla AA[SUP]4[/SUP], Rizzetto S[SUP]4[/SUP], Bull RA[SUP]4[/SUP], Qiu C[SUP]1[/SUP], Koutsakos M[SUP]2[/SUP], Clemens EB[SUP]2[/SUP], Loh L[SUP]2[/SUP], Chen T[SUP]1[/SUP], Liu L[SUP]1[/SUP], Cao P[SUP]5[/SUP], Ren Y[SUP]1[/SUP], Kedzierski L[SUP]2[/SUP], Kotsimbos T[SUP]6[/SUP], McCaw JM[SUP]5[/SUP], La Gruta NL[SUP]2,[/SUP][SUP]7[/SUP], Turner SJ[SUP]2,[/SUP][SUP]8[/SUP], Cheng AC[SUP]9[/SUP], Luciani F[SUP]4[/SUP], Zhang X[SUP]1[/SUP], Doherty PC[SUP]2,[/SUP][SUP]3[/SUP], Thomas PG[SUP]3[/SUP], Xu J[SUP]10[/SUP], Kedzierska K[SUP]11,[/SUP][SUP]12[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8[SUP]+[/SUP] T-cell profiles from patients hospitalized with avian H7N9, seasonal IAV, and influenza vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]PD-1[SUP]+[/SUP] CD8[SUP]+[/SUP] T cells, whereas the prolonged persistence of this set is found in ultimately fatal cases. Single-cell T cell receptor (TCR)-αβ analyses of activated CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells show similar TCRαβ diversity but differential clonal expansion kinetics in surviving and fatal H7N9 patients. Delayed clonal expansion associated with an early dichotomy at a transcriptome level (as detected by single-cell RNAseq) is found in CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells from patients who succumbed to the disease, suggesting a divergent differentiation pathway of CD38[SUP]+[/SUP]HLA-DR[SUP]+[/SUP]CD8[SUP]+[/SUP] T cells from the outset during fatal disease. Our study proposes that effective expansion of cross-reactive influenza-specific TCRαβ clonotypes with appropriate transcriptome signatures is needed for early protection against severe influenza disease.
PMID: 29483513 DOI: 10.1038/s41467-018-03243-7