The (gradual) rise of memory inflation

Klenerman, Paul

doi:10.1111/imr.12653

Cited by 71 publications

(73 citation statements)

References 94 publications

(314 reference statements)

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“…Thus, one possibility is that during the acute infection, there was accumulation of H7N9-specific CD8 ϩ T cells in the lungs but not in the blood in elderly patients and critically ill patients and that some of those cells recirculated to the blood over time. Another possible explanation is memory "inflation," which had been found in acute parvovirus B19 infections (33,34) and PARV4 infections (35) in humans; these settings have in common the long-term but low-level persistence of antigen (36). Persistence of H7N9 virus had been found in an HIV-infected patient (37).…”

Section: Discussionmentioning

confidence: 99%

Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection

Zhao

Chen

Tan

et al. 2018

J Virol

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Since 2013, influenza A H7N9 virus has emerged as the most common avian influenza virus subtype causing human infection, and it is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of 45 H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5 to 4 months, 6 to 8 months, and 12 to 15 months postinfection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to the intensive care unit (ICU) and patients presenting with acute respiratory distress syndrome (ARDS) than in patients with mild disease. Frequencies of virus-specific gamma interferon (IFN-γ)-secreting T cells were lower in critically ill patients requiring ventilation than in patients without ventilation within 4 months after infection. The percentages of H7N9-specific IFN-γ-secreting T cells tended to increase over time in patients ≥60 years or in critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8 T cells expressing the lung-homing marker CD49a were observed at 6 to 8 months after H7N9 infection compared to those in samples obtained at 1.5 to 4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients and have implications for T cell-directed immunization strategies. Avian influenza A H7N9 virus remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus-specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase over time in older and severely ill patients. Higher levels of antigen-specific CD8 T cells expressing the lung-homing marker CD49a were detected at 6 to 8 months after infection. Our results indicated a long-term impact of H7N9 infection on virus-specific memory T cells. These findings advance our understanding of the dynamics of virus-specific memory T cell immunity after H7N9 infection, which is relevant to the development of T cell-based universal influenza vaccines.

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Section: Discussionmentioning

confidence: 99%

Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection

Zhao

Chen

Tan

et al. 2018

J Virol

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“…Lifelong CMV infection is associated with a gradual expansion of T cells that have down-regulated classic costimulatory receptors (CD27, CD28) and up-regulated inhibitory receptors, such as KLRG1, and markers of terminal differentiation, such as CD57 (Klenerman, 2018). As the expansion of these cells has been associated with immunosenescence and reduced survival in CMV + elderly adults (Olsson et al, 2000;Pourgheysari et al, 2007), we assessed the proportions of T cells expressing these markers at baseline in the younger adults in this study.…”

Section: Memory T Cells In CMV + Young Adults Are Phenotypically Senementioning

confidence: 99%

Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

Bowyer

Sharpe

Venkatraman

et al. 2020

Journal of Experimental Medicine

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CMV is associated with immunosenescence and reduced vaccine responses in the elderly (>70 yr). However, the impact of CMV in young adults is less clear. In this study, healthy UK and Senegalese adults aged 18–50 yr (average, 29 yr) were vaccinated with the Ebola vaccine candidate chimpanzee adenovirus type 3–vectored Ebola Zaire vaccine (ChAd3-EBO-Z) and boosted with modified vaccinia Ankara Ebola Zaire–vectored (MVA–EBO-Z) vaccine. CMV carriage was associated with an expansion of phenotypically senescent CD4+ and CD8+ T cells expressing CD57 and killer cell lectin-like receptor G1 (KLRG1), which was negatively associated with vaccine responses in both cohorts. Ebola-specific T cell responses induced by vaccination also contained significantly increased frequencies of terminally differentiated CD57+KLRG1+ cells in CMV seropositive (CMV+) individuals. This study suggests that CMV can also affect vaccine responses in younger adults and may have a particularly marked impact in many developing countries where CMV seroprevalence is almost universal.

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“…Classically restricted HCMV-targeting CD8 + T cells are critical in the control of HCMV infection, and constitute up to 10% of the circulating T cell population during active infection [46,48,80], typically directed towards epitopes in the pp65 and IE peptides [81]. Infection with HCMV also establishes a 'memory inflation' population of CD8 + effector memory T cells (T EM ), which are defined by their large expansion after infection, terminally differentiated phenotype (CD57 + ) and their expression of CX3CR1 [81][82][83]. In CMV-seropositive individuals, a proportion of CD8 + T cells are HLA-Erestricted, long-lasting and express a T EM phenotype [83], although interact with the T cell receptor (TCR) with much lower affinity than HLA class Ia-bound peptides.…”

Section: Cytomegalovirusmentioning

confidence: 99%

HLA-E: exploiting pathogen-host interactions for vaccine development

Sharpe

Bowyer

Brackenridge

et al. 2019

Clinical and Experimental Immunology

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Summary Viruses, when used as vectors for vaccine antigen delivery, can induce strong cellular and humoral responses against target epitopes. Recent work by Hansen et al. describes the use of a cytomegalovirus‐vectored vaccine, which is able to generate a stable effector‐memory T cell population at the sites of vaccination in rhesus macaques. This vaccine, targeted towards multiple epitopes in simian immunodeficiency virus (SIV), did not induce classical CD8+ T cells. However, non‐canonical CD8+ T cell induction occurred via major histocompatibility complex (MHC) class II and MHC‐E. The MHC‐E‐restricted T cells could recognize broad epitopes across the SIV peptides, and conferred protection against viral challenge to 55% of vaccinated macaques. The human homologue, human leucocyte antigen (HLA)‐E, is now being targeted as a new avenue for vaccine development. In humans, HLA‐E is an unusually oligomorphic class Ib MHC molecule, in comparison to highly polymorphic MHC class Ia. Whereas MHC class Ia presents peptides derived from pathogens to T cells, HLA‐E classically binds defined leader peptides from class Ia MHC peptides and down‐regulates NK cell cytolytic activity when presented on the cell surface. HLA‐E can also restrict non‐canonical CD8+ T cells during natural infection with various pathogens, although the extent to which they are involved in pathogen control is mostly unknown. In this review, an overview is provided of HLA‐E and its ability to interact with NK cells and non‐canonical T cells. Also discussed are the unforeseen beneficial effects of vaccination, including trained immunity of NK cells from bacille Calmette–Guérin (BCG) vaccination, and the broad restriction of non‐canonical CD8+ T cells by cytomegalovirus (CMV)‐vectored vaccines in pre‐clinical trials.

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The (gradual) rise of memory inflation

Cited by 71 publications

References 94 publications

Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection

Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection

Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells

HLA-E: exploiting pathogen-host interactions for vaccine development

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