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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: 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]

In Argentina, more than 3 million people suffer from asthma, with numbers rising. When asthma patients acquire viral infections which, in turn, trigger the asthmatic response, they may develop subsequent bacterial infections, mainly by Streptococcus (S.) pneumoniae. This encapsulated Gram+ bacterium has been considered historically a T cell-independent antigen. Nevertheless, several papers describe the role of T cells in the immune response to S. pneumoniae. We evaluated the response to S. pneumoniae and compared it to the response to Mycobacterium (M.) tuberculosis, a different type of bacterium that requires a T helper type 1 ( Th1) response, in cells from atopic asthmatic children, to compare parameters for the same individual under exacerbation and in a stable situation whenever possible. We studied asthma patients and a control group of age-matched children, evaluating cell populations, activation markers and cytokine production by flow cytometry, and cytokine concentration in serum and cell culture supernatants by enzyme-linked immunosorbent assay ( ELISA). No differences were observed in γδ T cells for the same patient in either situation, and a tendency to lower percentages of CD4+ CD25hi T cells was observed under stability. A significantly lower production of tumour necrosis factor ( TNF)-α and a significantly higher production of interleukin ( IL)-5 was observed in asthma patients compared to healthy individuals, but no differences could be observed for IL-4, IL-13 or IL-10. A greater early activation response against M. tuberculosis, compared to S. pneumoniae, was observed in the asthmatic patients' cells. This may contribute to explaining why these patients frequently acquire infections caused by the latter bacterium and not the former. [ABSTRACT FROM AUTHOR]

T cell lines with defined cytokine profiles are an invaluable tool for assessing the control of immune responses both in vitro and in vivo. Production of such cell lines can be complex and time-consuming. Here we present a powerful technique to assay the cytokines produced by T cells activated polyclonally or with specific antigens. This paper presents a detailed methodology for the identification and isolation of cytokine-producing T cells activated with the artificial superantigen, CytoStim, or viral and fungal antigens. These cells can be analysed for different cytokines simultaneously, or cultured further to rapidly establish T cell lines making known cytokine types. We highlight the enumeration, isolation and phenotype of interleukin-17-producing T cells, and the rapid generation of virus-specific Th1 T cell lines. [ABSTRACT FROM AUTHOR]

The responses of thymocytes to Coneanavalin A (Con A), and interleukin 1 (IL-1), interleukin 2 (IL-2) and phorbol myristate acetate (PMA) were investigated. The enzyme 20-a-hydroxysteroid dehydrogenase (20αSDH) was used as a marker to distinguish between various populations of activated thymocytes. Thymocytes that were selected in Con A + pure or crude IL-2 expressed high 20αSDH activity, while those that were selected in Con A + recombinant IL-1 (rIL-1) or crude IL-1, or Con A + PMA expressed low 20αSDH activity. Both groups proliferate in response to Con A and had IL-2 receptors. After selection, the enzymatic phenotype was stable even if the cells were transferred from Con A + IL-2 to Con A + PMA (or IL-1) or vice versa. A third group was selected from thymocytes that were cultured in PMA + T cell growth factor (TCGF). This group expressed low levels of 20αSDH, had IL-2 receptors, but did not respond to Con A. This paper demonstrates that 20αSDH can be used as an enzymatic marker to distinguish between subpopulations of activated T cells, which have not been previously detected by the conventional surface markers. [ABSTRACT FROM AUTHOR]

Using in vivo assays for alloreactivity, the responsiveness of maternal lymph node cells was shown to be increased when cells were harvested from both syngeneically and allogeneically pregnant mice. In addition, foetal liver and thymus cells induced a state of delayed type hypersensitivity to alloantigens whereas trophoblastic tissue, in the form of 12 to 15 day metrial glands, did not. The influence of mouse placenta on in vitro immune responses was tested using 7-day ectoplacental cones as sources of trophoblastic tissue. Ectoplacental cones increased a T cell dependent but not a T cell independent antibody response, whereas T cell dependent cytotoxicity was reduced. The findings reported in this paper suggest that murine ectoplacental cones are a particularly useful tissue with which to study both specific and non-specific immunological activities of the trophoblast in syngeneic and allogeneic pregnancies. [ABSTRACT FROM AUTHOR]