15 research outputs found
Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection
Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen. Since the outbreak of the ongoing COVID-19 pandemic, a key question has focused on which SARS-CoV-2-specific T cells stimulated during acute infection give rise to long-lived memory T cells. Here, using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor sequencing, we longitudinally characterized individual SARS-CoV-2-specific CD8 T cells of patients with COVID-19 from acute infection to 1 year into recovery and found a distinct signature identifying long-lived memory CD8 T cells. SARS-CoV-2-specific memory CD8 T cells persisting 1 year after acute infection express CD45RA, IL-7 receptor-α and T cell factor 1, but they maintain low expression of CCR7, thus resembling CD45RA effector memory T cells. Tracking individual clones of SARS-CoV-2-specific CD8 T cells, we reveal that an interferon signature marks clones that give rise to long-lived cells, whereas prolonged proliferation and mechanistic target of rapamycin signalling are associated with clonal disappearance from the blood. Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8 T cells following an acute viral infection
Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2
The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B) cell subsets, including CD21 resting, CD21CD27 activated and CD21CD27 B cells. The interrelatedness between these B cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific B cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21 B cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specific immunization. At months 6 and 12 post-infection, CD21 resting B cells were the major B cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated B cell clones could redifferentiate upon antigen rechallenge into other B cell subsets, including CD21CD27 B cells, demonstrating that single B cell clones can adopt functionally different trajectories
Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course
Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1âyr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential
Autoantibodies against chemokines post-SARS-CoV-2 infection correlate with disease course
Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential
Signature of long-lived memory CD8+ T cells in acute SARS-CoV-2 infection
Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen1,2. Since the outbreak of the ongoing COVID-19 pandemic, a key question has focused on which SARS-CoV-2-specific T cells stimulated during acute infection give rise to long-lived memory T cells3. Here, using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor sequencing, we longitudinally characterized individual SARS-CoV-2-specific CD8+ T cells of patients with COVID-19 from acute infection to 1 year into recovery and found a distinct signature identifying long-lived memory CD8+ T cells. SARS-CoV-2-specific memory CD8+ T cells persisting 1 year after acute infection express CD45RA, IL-7 receptor-α and T cell factor 1, but they maintain low expression of CCR7, thus resembling CD45RA+ effector memory T cells. Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones that give rise to long-lived cells, whereas prolonged proliferation and mechanistic target of rapamycin signalling are associated with clonal disappearance from the blood. Collectively, we describe a transcriptional signature that marks long-lived, circulating human memory CD8+ T cells following an acute viral infection.ISSN:0028-0836ISSN:1476-468
CD8+ T cell signature in acute SARS-CoV-2 infection identifies memory precursors
Immunological memory is a hallmark of adaptive immunity and facilitates an accelerated and enhanced immune response upon re-infection with the same pathogen1,2. Since the outbreak of the ongoing coronavirus disease 19 (COVID-19) pandemic, a key question has focused on whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells stimulated during acute infection give rise to long-lived memory T cells3. Using spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor (TCR) sequencing we longitudinally characterize individual SARS-CoV-2-specific CD8+ T cells of COVID-19 patients from acute infection to one year into recovery and find a distinct signature identifying long-lived memory CD8+ T cells. SARS-CoV-2-specific memory CD8+ T cells persisting one year after acute infection re-express CD45RA and interleukin-7 receptor α (CD127), upregulate T cell factor-1 (TCF1), and maintain low CCR7, thus resembling CD45RA+ effector-memory T (TEMRA) cells. Tracking individual clones of SARS-CoV-2-specific CD8+ T cells, we reveal that an interferon signature marks clones giving rise to long-lived cells, whereas prolonged proliferation and mammalian target of rapamycin (mTOR) signaling are associated with clone contraction and disappearance. Collectively, we identify a transcriptional signature differentiating short-from long-lived memory CD8+ T cells following an acute virus infection in humans
Fate and plasticity of SARS-CoV-2-specific B cells during memory and recall response in humans
B cell responses to different pathogens recruit tailored effector mechanisms, resulting in functionally specialized subsets. For human memory B cells (MBCs), these include CD21+ resting, CD21âCD27+ activated, and CD21âCD27â atypical cells. Whether these subsets follow deterministic or interconnected fates is unknown. We demonstrate in COVID-19 patients that single clones of SARS-CoV-2-specific MBCs followed multiple fates with distinctive phenotypic and functional characteristics. 6â12 months after infection, most circulating MBCs were CD21+ resting cells, which also accumulated in peripheral lymphoid organs where they acquired markers of tissue residency. Conversely, at acute infection and following SARS-CoV-2-specific immunization, CD21â MBCs became the predominant subsets, with atypical MBCs expressing high T-bet, inhibitory molecules, and distinct chemokine receptors. B cell receptor sequencing allowed tracking of individual MBC clones differentiating into CD21+, CD21âCD27+, and CD21âCD27â cell fates. Collectively, single MBC clones can adopt functionally different trajectories, thus contributing to immunity to infection
Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2
The B cell response to diferent pathogens uses tailored efector mechanisms and results in functionally specialized memory B (Bâ) cell subsets, including CD21âș resting, CD21â»CD27âș activated and CD21â»CD27â»Bâ cells. The interrelatedness between these Bâ cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specifc Bâ cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21â»Bâ cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specifc immunization. At months 6 and 12 post-infection, CD21âș resting Bâ cells were the major Bâ cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated Bâ cell clones could rediferentiate upon antigen rechallenge into other Bâ cell subsets, including CD21â»CD27â»Bâ cells, demonstrating that single Bâ cell clones can adopt functionally diferent trajectories.ISSN:1529-2908ISSN:1529-291
Publisher Correction: Human memory B cells show plasticity and adopt multiple fates upon recall response to SARS-CoV-2
ISSN:1529-2908ISSN:1529-291
T-cell recovery and evidence of persistent immune activation 12 months after severe COVID-19
Background
T-cell lymphopenia and functional impairment is a hallmark of severe acute coronavirus disease 2019 (COVID-19). How T-cell numbers and function evolve at later timepoints after clinical recovery remains poorly investigated.
Methods
We prospectively enrolled and longitudinally sampled 173 individuals with asymptomatic to critical COVID-19 and analyzed phenotypic and functional characteristics of T cells using flow cytometry, 40-parameter mass cytometry, targeted proteomics, and functional assays.
Results
The extensive T-cell lymphopenia observed particularly in patients with severe COVID-19 during acute infection had recovered 6âmonths after infection, which was accompanied by a normalization of functional T-cell responses to common viral antigens. We detected persisting CD4+ and CD8+ T-cell activation up to 12âmonths after infection, in patients with mild and severe COVID-19, as measured by increased HLA-DR and CD38 expression on these cells. Persistent T-cell activation after COVID-19 was independent of administration of a COVID-19 vaccine post-infection. Furthermore, we identified a subgroup of patients with severe COVID-19 that presented with persistently low CD8+ T-cell counts at follow-up and exhibited a distinct phenotype during acute infection consisting of a dysfunctional T-cell response and signs of excessive pro-inflammatory cytokine production.
Conclusion
Our study suggests that T-cell numbers and function recover in most patients after COVID-19. However, we find evidence of persistent T-cell activation up to 12âmonths after infection and describe a subgroup of severe COVID-19 patients with persistently low CD8+ T-cell counts exhibiting a dysregulated immune response during acute infection.ISSN:0105-4538ISSN:1398-999