Long-term and short-term immunity to SARS-CoV-2: Why it matters

The adaptive immune system, regulated by CD4 T cells, is essential for control of many viral infections. Endemic coronavirus infections generally occur as short-term upper respiratory tract infections which in many cases appear to be cleared before adaptive immunity is fully involved, since adaptive immunity takes approximately 1.5-2 weeks to ramp up the response to a primary infection, or approximately 1 week for a recurrent infection. However, the adaptive immune response to SARS-CoV-2 infection will be critical to full recovery with minimal long-lasting effects, and to either prevention of recurrence of infection or at least reduced severity of symptoms. The detailed kinetics of this infection versus the dynamics of the immune response, including in vaccinated individuals, will largely determine these outcomes

CD4(+) T follicular helper and IgA(+) B cell numbers in gut biopsies from HIV-infected subjects on antiretroviral therapy are similar to HIV-uninfected individuals

BACKGROUND: Disruption of gastrointestinal tract epithelial and immune barriers contribute to microbial translocation, systemic inflammation, and progression of HIV-1 infection. Antiretroviral therapy (ART) may lead to reconstitution of CD4(+) T cells in gut-associated lymphoid tissue (GALT), but its impact on humoral immunity within GALT is unclear. Therefore, we studied CD4(+) subsets, including T follicular helper cells (Tfh), as well as resident B cells that have switched to IgA production, in gut biopsies, from HIV(+) subjects on suppressive ART compared to HIV-negative controls (HNC). METHODS: Twenty-three HIV(+) subjects on ART and 22 HNC undergoing colonoscopy were recruited to the study. Single-cell suspensions were prepared from biopsies from left colon (LC), right colon (RC), and terminal ileum (TI). T and B lymphocyte subsets, as well as EpCAM(+) epithelial cells, were accurately enumerated by flow cytometry, using counting beads. RESULTS: No significant differences in the number of recovered epithelial cells were observed between the two subject groups. However, the median TI CD4(+) T cell count/10(6) epithelial cells was 2.4-fold lower in HIV(+) subjects versus HNC (19,679 versus 47,504 cells; p = 0.02). Similarly, median LC CD4(+) T cell counts were reduced in HIV(+) subjects (8,358 versus 18,577; p = 0.03) but were not reduced in RC. Importantly, we found no significant differences in Tfh or IgA(+) B cell counts at either site between HIV(+) subjects and HNC. Further analysis showed no difference in CD4(+), Tfh, or IgA(+) B cell counts between subjects who commenced ART in primary compared to chronic HIV-1 infection. Despite the decrease in total CD4 T cells, we could not identify a selective decrease of other key subsets of CD4(+) T cells, including CCR5(+) cells, CD127(+) long-term memory cells, CD103(+) tissue-resident cells, or CD161(+) cells (surrogate marker for Th17), but there was a slight increase in the proportion of T regulatory cells. CONCLUSION: While there were lower absolute CD4(+) counts in the TI and LC in HIV(+) subjects on ART, they were not associated with significantly reduced Tfh cell counts or IgA(+) B cells, suggesting that this important vanguard of adaptive immune defense against luminal microbial products is normalized following ART.John Zaunders, Mark Danta, Michelle Bailey, Gerald Mak, Katherine Marks, Nabila Seddiki, Yin Xu, David J. Templeton, David A. Cooper, Mark A. Boyd, Anthony D. Kelleher and Kersten K. Koelsc

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Circulating gluten-specific FOXP3 + CD39 + regulatory T cells have impaired suppressive function in patients with celiac disease

Background Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. Objective We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3)+ Treg cells. Methods Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4+ T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4+ T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Results Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4+ T cells were FOXP3+CD39+ Treg cells, which reside within the pool of memory CD4+CD25+CD127lowCD45RO+ Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3+CD39+ Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. Conclusion This study provides the first estimation of FOXP3+CD39+ Treg cell frequency within circulating gluten-specific CD4+ T cells after oral gluten challenge of patients with celiac disease. FOXP3+CD39+ Treg cells comprised a major proportion of all circulating gluten-specific CD4+ T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key contributor to disease pathogenesis

Quantum-Amplified Simultaneous Quantum-Classical Communications

Classical free-space optical (FSO) communication promises massive data throughput rates relative to traditional wireless technologies - an attractive outcome now being pursued in the context of satellite-ground, inter-satellite and deep-space communications. The question we investigate here is: how can we minimally alter classical FSO systems, both in infrastructure and in energy input, to provide some element of quantum communication coexisting with classical communications? To address this question, we explore additional Gaussian displacements to classical FSO encoding on the satellite, determining the minimum signal requirements that will meet given specifications on the combined classical and quantum communications throughput. We then investigate whether enhanced quantum-based amplifiers embedded in receivers, which have proven advantageous in standalone quantum communication, can enhance our combined classical-quantum communication throughput. We show how this is indeed the case, but only at the cost of some additional receiver complexity, relative to standalone quantum communications. This additional complexity takes the form of an additional beamsplitter and two heterodyne detectors at the receiver. Our results illustrate a viable pathway to realising quantum communication from classical FSO systems with minimal design changes.Comment: 10 pages, 5 figures. Accepted for publication in IEEE QCNC 2024 conference proceeding

Editorial: Cytotoxic CD4+ T Cells in Viral Infections

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