Herpes Zoster in the Older Adult John, Amrita R; Canaday, David H
Infectious disease clinics of North America,
12/2017, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Herpes zoster (HZ) is the result of reactivation of latent varicella zoster virus (VZV) and occurs most frequently in older adults. Classically, HZ presents as a unilateral, selflimited, dermatomal ...rash. Postherpetic neuralgia (PHN) is a common sequela, presenting as severe pain that persists after the rash has resolved. In the elderly, PHN can be debilitating and requires a prompt diagnosis, treatment with antivirals, and adequate pain control. A longer-term pain management strategy is required if PHN occurs. A modestly effective vaccine exists and is recommended for older individuals.
Abstract
After BNT162b2 messenger RNA vaccination, antibody levels to spike, receptor-binding domain, and virus neutralization were examined in 149 nursing home residents and 110 healthcare worker ...controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–naive nursing home residents’ median post–second vaccine dose antibody neutralization titers are one-quarter that of SARS-CoV-2–naive healthcare workers.
The global coronavirus pandemic is unlike any other since 1918. A century of dramatic medical advances has produced a public expectation that the medical field will rapidly provide solutions to ...restore normalcy. In less than 6 months, since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified, the massive international effort to develop a SARS-CoV-2 vaccine has generated more than 140 vaccines in different stages of development, with 9 already recruiting into clinical trials posted on ClinicalTrials.gov. The long-term strategy to handle coronavirus disease 2019 (COVID-19) will almost certainly rely on vaccines. But what type of protection can we realistically expect to achieve from vaccines and when?
Elimination of lymphoid tissue reservoirs is a key component of HIV eradication strategies. CD8+ T cells play a critical role in control of HIV, but their functional attributes in lymph nodes (LNs) ...remain unclear. Here, we show that memory, follicular CXCR5+, and HIV-specific CD8+ T cells from LNs do not manifest the properties of cytolytic CD8+ T cells. While the frequency of follicular CXCR5+ CD8+ T cells was strongly inversely associated with peripheral viremia, this association was not dependent on cytolytic CXCR5+ CD8+ T cells. Moreover, the poor cytolytic activity of LN CD8+ T cells was linked to a compartmentalized dissociation between effector programming and the transcription factor T-bet. In line with this, activation of LN CD8+ T cells only partially induced the acquisition of cytolytic functions relative to peripheral blood CD8+ T cells. These results suggest that a state of immune privilege against CD8+ T cell-mediated cytolysis exists in lymphoid tissue, potentially facilitating the persistence of HIV.
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•CD8+ T cells in quiescent lymphoid tissues do not express markers of cytotoxicity•Lymphoid tissue HIV-specific CD8+ T cells do not possess full cytolytic markers•Noncytolytic CXCR5+ CD8+ T cells in lymphoid tissue associate with viral control
Reuter et al. show that lymphoid tissue CD8+ T cells from HIV-infected and uninfected individuals do not possess phenotypic, functional, or transcriptional regulatory properties of cytolytic T cells equivalent to those found in circulation. Their findings suggest that the failure to eliminate HIV could be related to compartmentalized CD8+ T cell function favoring noncytolytic responses in lymphoid tissue.
Abstract
Background
Influenza leads in preventable infection-related hospitalization in nursing home (NH) residents. The adjuvanted trivalent influenza vaccine (aTIV) is more immunogenic than ...similarly dosed nonadjuvanted trivalent influenza vaccine (TIV), and observational studies suggest aTIV better prevents hospitalizations in older adults. We prospectively tested this in an NH setting.
Methods
NHs with ≥50 long-stay residents aged ≥65 years were randomized to offer aTIV or TIV for residents for the 2016–2017 influenza season. Using intent-to-treat resident-level analysis with Cox proportional hazards regression models adjusted for clustering by facility and a priori baseline covariates (eg, age, heart failure, and facility-level characteristics), we assessed relative aTIV:TIV effectiveness for hospitalization (ie, all-cause, respiratory, and pneumonia and influenza P&I).
Results
We randomized 823 NHs, housing 50 012 eligible residents, to aTIV or TIV. Residents were similar between groups by age (mean, ~79 years), heart failure, lung disease, and influenza and pneumococcal vaccine uptake, except aTIV homes housed fewer Black residents (14.5 vs 18.9%). Staff vaccine uptake was similar (~55%). P&I and all-cause resident hospitalization rates were lower (adjusted HR aHR, .80 95% CI, .66–.98; P = .03 and .94 .89–.99; P = .02, respectively) for aTIV versus TIV, while the respiratory hospitalization rate was similar, in a season where vaccine effectiveness was considered poor.
Conclusions
aTIV was more effective than TIV in preventing all-cause and P&I hospitalization from NHs during an A/H3N2-predominant season when TIV was relatively ineffective.
Clinical Trials Registration
NCT02882100.
This trial evaluates adjuvanted influenza vaccine (aTIV) and hospitalization using an innovative pragmatic, cluster-randomized trial design in a high-risk nursing home population. aTIV was more effective than standard influenza vaccine in preventing all-cause hospitalization from US nursing homes.
Institutionalized and community-dwelling older adults have been greatly impacted by the coronavirus disease 2019 (COVID-19) pandemic with increased morbidity and mortality. The advent of vaccines and ...their widespread use in this population has brought about a dramatic turnaround in COVID-19 outcomes. The immunogenicity and effectiveness of the various vaccine options worldwide are discussed. Optimization of vaccine usage will still be important to maximize protection due to reduced initial immunity, development of variant strains, and fading of immunity over time. There are also lessons learned specific to older populations for future pandemics of novel pathogens.
T follicular regulatory (Tfr) cells are a population of CD4
T cells that express regulatory T cell markers and have been shown to suppress humoral immunity. However, the precise mechanisms and ...location of Tfr-mediated suppression in the lymph node (LN) microenvironment are unknown. Using highly multiplexed quantitative imaging and functional assays, we examined the spatial distribution, suppressive function, and preferred interacting partners of Tfr cells in human mesenteric LNs. We find that the majority of Tfr cells express low levels of PD-1 and reside at the border between the T cell zone and B cell follicle, with very few found in the germinal centers (GCs). Although PD-1
Tfr cells expressed higher levels of CD38, CTLA-4, and GARP than PD-1
Tfr cells, both potently suppressed antibody production in vitro. These findings highlight the phenotypic diversity of human Tfr cells and suggest that Tfr-mediated suppression is most efficient at the T-B border and within the follicle, not in the GC.
T follicular helper cells (Tfh), a subset of CD4+ T cells, provide requisite help to B cells in the germinal centers (GC) of lymphoid tissue. GC Tfh are identified by high expression of the chemokine ...receptor CXCR5 and the inhibitory molecule PD-1. Although more accessible, blood contains lower frequencies of CXCR5+ and PD-1+ cells that have been termed circulating Tfh (cTfh). However, it remains unclear whether GC Tfh exit lymphoid tissues and populate this cTfh pool. To examine exiting cells, we assessed the phenotype of Tfh present within the major conduit of efferent lymph from lymphoid tissues into blood, the human thoracic duct. Unlike what was found in blood, we consistently identified a CXCR5-bright PD-1-bright (CXCR5BrPD-1Br) Tfh population in thoracic duct lymph (TDL). These CXCR5BrPD-1Br TDL Tfh shared phenotypic and transcriptional similarities with GC Tfh. Moreover, components of the epigenetic profile of GC Tfh could be detected in CXCR5BrPD-1Br TDL Tfh and the transcriptional imprint of this epigenetic signature was enriched in an activated cTfh subset known to contain vaccine-responding cells. Together with data showing shared TCR sequences between the CXCR5BrPD-1Br TDL Tfh and cTfh, these studies identify a population in TDL as a circulatory intermediate connecting the biology of Tfh in blood to Tfh in lymphoid tissue.
B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and ...functional properties of T-bet+ and T-bet− memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet− and T-bet+ hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet− and T-bet+ MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet+ MBCs could be subdivided into recirculating T-betlo MBCs and spleen-resident T-bethi MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.
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•T-bet+ B cells are a separate and durable memory subset in mice and humans•T-bethi memory B cells are absent from the lymphatic circulation•Influenza-specific T-bethi memory B cells are spleen-resident in mice•B cell-intrinsic T-bet is required for >90% of flu- and HA stalk-specific antibodies
Johnson, Rosenthal, Knox, Myles, et al. find that differential T-bet expression marks subsets of memory B cells (MBCs) with distinct homing and tissue residency patterns and functional properties. Distinguishing features of T-bet−, T-bethi, and T-betlo MBCs are seen also in humans.
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