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Summary: The immune system plays a critical role in protecting the host against infection but is subject to numerous levels of control that are necessary to prevent pathological, tissue-damaging responses. Inappropriate inflammatory immune responses to self-antigens, innocuous commensal microorganisms, or environmental antigens can lead to chronic, debilitating, and degenerative diseases. Regulatory T cells have an essential, non-redundant, and dominant function in preventing pathological immune responses, as shown by the development of systemic fatal autoimmunity in humans and animals with a genetic deficiency in regulatory T cells. In addition to controlling immune responses, there is a growing understanding that regulatory T cells also contribute directly to tissue homeostasis by promoting tissue regeneration and repair. For these reasons, the prospect of enhancing regulatory T-cell numbers and/or function in patients represents an appealing therapeutic opportunity with potential applications in many diseases, including some where the pathological role of the immune system has only recently been recognized. Approaches to enhance regulatory T cells are now starting to be explored in clinical studies in humans. This review series brings together papers highlighting the Treg-enhancing approaches that are most advanced clinically and examples of therapeutic opportunities based on our growing understanding of regulatory T-cell functions. [ABSTRACT FROM AUTHOR]

Understanding the T-cell response to SARS-CoV-2 is key in patients who lack antibody production. We demonstrate the applicability of a functional assay to measure the T-cell response in a cohort of patients with immunodeficiency. T-cell responses to COVID are now linked to improved outcomes. This paper demonstrates a method to robustly test responses for routine diagnostic use in healthy controls and those unable to make a detectable antibody response due to underlying immune deficiency (primary or acquired). [ABSTRACT FROM AUTHOR]

Summary: Ageing dramatically affects number and function of both innate and adaptive arms of immune system, particularly T cell subsets, contributing to reduced vaccination efficacy, decreased resistance to infections and increased prevalence of cancer in older people. In the present paper, we analysed the age‐related changes in the absolute number of lymphocytes in 214 Sicilian subjects, and in the percentages of T and natural killer (NK) cells in a subcohort of donors. We compared these results with the immunophenotype of the oldest living Italian supercentenarian (aged 111 years). The results were also sorted by gender. The correlation between number/percentage of cells and age in all individuals. and separately in males and females, was examined using a simple linear regression analysis. We did not record the increase in the rate of inversion of the CD4/CD8 ratio, frequently reported as being associated with ageing in literature. Our observation was the direct consequence of a flat average trend of CD4+ and CD8+ T cell percentages in ageing donors, even when gender differences were included. Our results also suggest that CD4+ and CD8+ subsets are not affected equally by age comparing females with males, and we speculated that gender may affect the response to cytomegalovirus (CMV) infection. The supercentenarian showed a unique immunophenotypic signature regarding the relative percentages of her T cell subsets, with CD4+ and CD8+ T cell percentages and CD4+ naive T cell values in line with those recorded for the octogenarian subjects. This suggests that the supercentenarian has a naive 'younger' T cell profile comparable to that of a >80‐year‐old female. [ABSTRACT FROM AUTHOR]

Summary: The factors responsible for the spectrum of coronavirus 19 (COVID‐19) disease severity and the genesis and nature of protective immunity against COVID‐19 remain elusive. Multiple studies have investigated the immune responses to COVID‐19 in various populations, including those without evidence of COVID‐19 infection. Information regarding innate and adaptive immune responses to the novel severe respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has evolved rapidly. Data are accumulating defining disease phenotypes that aid in rational and informed development of new therapeutic approaches for the treatment of patients infected with SARS‐CoV‐2 and the development of novel vaccines. In this paper, data on important innate immune responses are summarized, including cytokines, specifically interleukin (IL)‐6 and complement, and potential treatments are explored. Adaptive immune responses and derivative therapeutics such as monoclonal antibodies directed at spike proteins are also examined. Finally, data on real‐time assessments of adaptive immune responses are explored, which include CD4+/CD8+ T cells, natural killer (NK) T cells, memory B cells and T follicular cells with specificities for COVID‐19 peptides in infected and normal individuals. Data of two novel vaccines have been released, both showing > 95% efficacy in preventing SARS‐CoV‐2 infection. Analysis of humoral and cellular responses to the vaccines will determine the robustness and durability of protection. In addition, long‐term assessment of SARS‐CoV‐2 memory B and T cell‐mediated immune responses in patients recovering from an infection or those with cross‐reactive immunological memory will help to define risk for future SARS‐CoV infections. Finally, patients recovering from SARS‐CoV‐2 infection may experience prolonged immune activation probably due to T cell exhaustion. This will be an important new frontier for study. This review summarizes published data on the relevant innate and adaptive immune responses to SARS‐CoV‐2. Data characterizing innate and adaptive immune responses have rapidly led to informed therapeutic interventions, including vaccine development and recognition of dysfunctional immune responses that are likely responsible for post‐COVID‐19 autoimmunity. [ABSTRACT FROM AUTHOR]