Control of Immunity by the Microbiota

2021 ◽  
Vol 39 (1) ◽  
pp. 449-479
Author(s):  
Eduard Ansaldo ◽  
Taylor K. Farley ◽  
Yasmine Belkaid
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Microbial Communities ◽  
Adaptive Immunity ◽  
Immune Recognition ◽  
T Helper ◽  
Cell Responses ◽  
Temporal Windows

The immune system has coevolved with extensive microbial communities living on barrier sites that are collectively known as the microbiota. It is increasingly clear that microbial antigens and metabolites engage in a constant dialogue with the immune system, leading to microbiota-specific immune responses that occur in the absence of inflammation. This form of homeostatic immunity encompasses many arms of immunity, including B cell responses, innate-like T cells, and conventional T helper and T regulatory responses. In this review we summarize known examples of innate-like T cell and adaptive immunity to the microbiota, focusing on fundamental aspects of commensal immune recognition across different barrier sites. Furthermore, we explore how this cross talk is established during development, emphasizing critical temporal windows that establish long-term immune function. Finally, we highlight how dysregulation of immunity to the microbiota can lead to inflammation and disease, and we pinpoint outstanding questions and controversies regarding immune system–microbiota interactions.

scholarly journals Reduction of Retrovirus-Induced Immunosuppression by In Vivo Modulation of T Cells during Acute Infection

2004 ◽  
Vol 78 (21) ◽  
pp. 11641-11647 ◽  
Author(s):  
Hong He ◽  
Ronald J. Messer ◽  
Shimon Sakaguchi ◽  
Guojun Yang ◽  
Shelly J. Robertson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Acute Infection ◽  
Tumor Necrosis Factor Receptor ◽  
Cell Responses ◽  
Th1 Immune Responses ◽  
Necrosis Factor

ABSTRACT Chronic infection with Friend retrovirus is associated with suppressed antitumor immune responses. In the present study we investigated whether modulation of T-cell responses during acute infection would restore antitumor immunity in persistently infected mice. T-cell modulation was done by treatments with DTA-1 anti- glucocorticoid-induced tumor necrosis factor receptor monoclonal antibodies. The DTA-1 monoclonal antibody is nondepleting and delivers costimulatory signals that both enhance the activation of effector T cells and inhibit suppression by regulatory T cells. DTA-1 therapy produced faster Th1 immune responses, significant reductions in both acute virus loads and pathology and, most importantly, long-term improvement of CD8+ T-cell-mediated antitumor responses.

scholarly journals Bias of the Immune Response to Pneumocystis murina Does Not Alter the Ability of Neonatal Mice to Clear the Infection

2021 ◽  
Vol 7 (10) ◽  
pp. 827
Author(s):  
Cathryn Kurkjian ◽  
Melissa Hollifield ◽  
David J. Feola ◽  
Beth A. Garvy
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
T Helper ◽  
Newborn Mice ◽  
Robust Immune Response ◽  
Cell Responses ◽  
Neonatal Mice ◽  
Th1 Cytokine ◽  
Specific Igg

Newborn mice are unable to clear Pneumocystis (PC) infection with the same efficiency as adults due, in part, to their inability to develop a robust immune response to infection until three weeks of age. It is known that infants tend develop a Th2 skewed response to antigen so we sought to determine whether a biased cytokine response altered the clearance of PC infection in neonatal mice. P. murina infection in neonatal mice resulted in increased IL-4 expression by CD4 T cells and myeloid cells, augmented IL-13 secretion within the airways and increased arginase activity in the airways, indicative of Th2-type responses. P. murina-infected IL-4Rα−/− neonates had a shift towards Th1 cytokine production and increased numbers of CD4 and CD8 T cells within the lung as well as elevated levels of P. murina-specific IgG. IFNγ−/− and IL-23 p19−/− mice had altered CD4-T cell-dependent cytokine and cell responses. Though we could alter the T helper cell environment in neonatal knockout mice, there was no loss in the ability of these pups to clear infection. It is possible that the Th2 phenotype normally seen in neonatal mice protects the developing lung from pro-inflammatory immune responses without compromising host defense against P. murina.

scholarly journals One Year after Mild COVID-19: The Majority of Patients Maintain Specific Immunity, But One in Four Still Suffer from Long-Term Symptoms

2021 ◽  
Vol 10 (15) ◽  
pp. 3305
Author(s):  
Andreas Rank ◽  
Athanasia Tzortzini ◽  
Elisabeth Kling ◽  
Christoph Schmid ◽  
Rainer Claus ◽  
...  
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Early Time ◽  
T Helper ◽  
Persistent Symptoms ◽  
Cell Responses ◽  
One Year ◽  
Antibody Levels

After COVID-19, some patients develop long-term symptoms. Whether such symptoms correlate with immune responses, and how long immunity persists, is not yet clear. This study focused on mild COVID-19 and investigated correlations of immunity with persistent symptoms and immune longevity. Persistent complications, including headache, concentration difficulties and loss of smell/taste, were reported by 51 of 83 (61%) participants and decreased over time to 28% one year after COVID-19. Specific IgA and IgG antibodies were detectable in 78% and 66% of participants, respectively, at a 12-month follow-up. Median antibody levels decreased by approximately 50% within the first 6 months but remained stable up to 12 months. Neutralizing antibodies could be found in 50% of participants; specific INFgamma-producing T-cells were present in two thirds one year after COVID-19. Activation-induced marker assays identified specific T-helper cells and central memory T-cells in 80% of participants at a 12-month follow-up. In correlative analyses, older age and a longer duration of the acute phase of COVID-19 were associated with higher humoral and T-cell responses. A weak correlation between long-term loss of taste/smell and low IgA levels was found at early time points. These data indicate a long-lasting immunological memory against SARS-CoV-2 after mild COVID-19.

scholarly journals Effective and Long-Lasting Immunity against the Parasite Leishmania major in CD8-Deficient Mice

1998 ◽  
Vol 66 (8) ◽  
pp. 3968-3970 ◽  
Author(s):  
Magdalena Huber ◽  
Emma Timms ◽  
Tak W. Mak ◽  
Martin Röllinghoff ◽  
Michael Lohoff
Keyword(s):  
T Cells ◽  
Primary Infection ◽  
Leishmania Major ◽  
T Helper ◽  
T Helper 1 ◽  
Cell Responses ◽  
Deficient Mice ◽  
Parasite Leishmania

ABSTRACT The results of earlier investigations that tested whether CD8+ T cells are required in the defense againstLeishmania major have been inconsistent. We used CD8-deficient mice to directly address this issue. After primary infection with L. major, CD8-deficient mice controlled the infection for over 1 year and mounted strong T helper 1 cell responses. Thus, CD8+ T cells are not required for the long-term control of a primary infection with L. major.

scholarly journals Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2233 ◽  
Author(s):  
Nicole Brooks ◽  
Jennifer Hsu ◽  
Sandra Esparon ◽  
Dodie Pouniotis ◽  
Geoffrey Pietersz
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Tandem Repeat ◽  
T Cell Responses ◽  
Variable Number ◽  
T Helper ◽  
Cell Responses ◽  
Helper Epitope ◽  
Cell Penetrating

Peptide-based vaccines for cancer have many advantages however, for optimization these immunogens should incorporate peptide epitopes that induce CD8, as well as CD4 responses, antibody and long term immunity. Cell penetrating peptides (CPP) with a capacity of cytosolic delivery have been used to deliver antigenic peptides and proteins to antigen presenting cells to induce cytotoxic T cell, helper T cell and humoral responses in mice. For this study, a tripartite CPP including a mucin 1 (MUC1) variable number of tandem repeat (VNTR) containing multiple T cell epitopes and tetanus toxoid universal T helper epitope peptide (tetCD4) was synthesised (AntpMAPMUC1tet) and immune responses investigated in mice. Mice vaccinated with AntpMAPMUC1tet + CpG show enhanced antigen-specific interferon-gamma (IFN-γ) and IL-4 T cell responses compared with AntpMAPMUC1tet vaccination alone and induced a Th1 response, characterised by a higher ratio of IgG2a antibody/IgG1 antibodies. Furthermore, vaccination generated long term MUC1-specific antibody and T cell responses and delayed growth of MUC1+ve tumours in mice. This data demonstrates the efficient delivery of branched multiple antigen peptides incorporating CPP and that the addition of CpG augments immune responses.

scholarly journals Immune system derived from homeostatic proliferation generates normal CD8 T-cell memory but altered repertoires and diminished heterologous immune responses

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 680-689 ◽  
Author(s):  
Sue-Jane Lin ◽  
Alex T. Chen ◽  
Raymond M. Welsh
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Homeostatic Proliferation ◽  
Memory Cells ◽  
Cell Repertoire ◽  
Cell Responses

AbstractThe host responds to lymphopenic environments by acute homeostatic proliferation of T lymphocytes, which acquire phenotypes similar to memory cells. Using T-cell knockout (KO) mice adoptively reconstituted with splenocytes from immunologically naive mice, we examined the immune responses of an immune system derived from homeostatically proliferating (HP) T cells. HP cells mounted relatively normal acute CD8 T-cell responses to lymphocytic choriomeningitis virus (LCMV), but with altered T-cell receptor (TCR) repertoires, and they became functional memory cells capable of recall responses. Although homeostatic proliferation does not normally fully restore T-cell numbers, the CD8+ T-cell pool was completely restored in T-cell KO mice after LCMV infection. CD4 T-cell responses were lower and not fully restored but seemed sufficient to allow for complete differentiation of CD8 memory T cells. The LCMV-immune HP mouse had an immune repertoire heavily biased with LCMV epitope-specific T cells with oligoclonal expansions. LCMV-immune HP mice had reduced cross-reactive and non–cross-reactive CD8 T-cell responses when challenged with a T cell–cross-reactive virus. Thus, whereas an HP immune system is capable of mounting relatively normal acute and memory CD8 T-cell responses, the narrowing of the T-cell repertoire may reduce immune responses to subsequently encountered pathogens.

Therapeutic potential of immunostimulatory monoclonal antibodies

2006 ◽  
Vol 111 (2) ◽  
pp. 93-106 ◽  
Author(s):  
Juliet C. Gray ◽  
Peter W. M. Johnson ◽  
Martin J. Glennie
Keyword(s):  
Monoclonal Antibodies ◽  
Immune System ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
New Approach ◽  
Advantages And Disadvantages ◽  
Cell Responses ◽  
Enhance Antigen Presentation

The aim of cancer immunotherapy is to employ the specificity of the immune system to provide a more effective, less toxic, treatment compared with conventional therapies. Although many strategies have been used to try to generate effective anticancer immune responses, very few have reached mainstream clinical use. A new approach introduced over the last few years is to use immunostimulatory mAbs (monoclonal antibodies) to boost weak endogenous antitumour immune responses to levels which are therapeutic. Such agonistic or antagonistic mAbs bind to key receptors in the immune system acting to enhance antigen presentation, provide co-stimulation or to counteract immunoregulation. In animal models, this approach has been shown to promote powerful tumour-specific T-cell responses capable of clearing established tumour and leaving the animal with long-term immunity. In addition to this impressive therapy seen in tumour models, these same mAbs also have the potential to be therapeutically useful in autoimmune and infectious diseases. This review discusses the use of these mAbs as therapeutic agents, their advantages and disadvantages and the challenges that need to be overcome to use them clinically.

scholarly journals Long-term protective immunity induced by an adjuvant-containing live-attenuated AIDS virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomotaka Okamura ◽  
Yuya Shimizu ◽  
Masamitsu N. Asaka ◽  
Tomohiro Kanuma ◽  
Yusuke Tsujimura ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Immune Responses ◽  
Protective Immunity ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Aids Virus ◽  
Cynomolgus Macaques ◽  
Cd8 Depletion

AbstractThe use of an adjuvant in vaccination is thought to be effective for enhancing immune responses to various pathogens. We genetically constructed a live attenuated simian human immunodeficiency virus (SHIV) to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When the macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B had become undetectable, SHIV89.6P was not detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of the pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.

scholarly journals Successful Interference with Cellular Immune Responses to Immunogenic Proteins Encoded by Recombinant Viral Vectors

2001 ◽  
Vol 75 (1) ◽  
pp. 269-277 ◽  
Author(s):  
Adelaida Sarukhan ◽  
Sabine Camugli ◽  
Bernard Gjata ◽  
Harald von Boehmer ◽  
Olivier Danos ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Gene Transfer ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cellular Immune Responses ◽  
Cellular Immune

ABSTRACT Vectors derived from the adeno-associated virus (AAV) have been successfully used for the long-term expression of therapeutic genes in animal models and patients. One of the major advantages of these vectors is the absence of deleterious immune responses following gene transfer. However, AAV vectors, when used in vaccination studies, can result in efficient humoral and cellular responses against the transgene product. It is therefore important to understand the factors which influence the establishment of these immune responses in order to design safe and efficient procedures for AAV-based gene therapies. We have compared T-cell activation against a strongly immunogenic protein, the influenza virus hemagglutinin (HA), which is synthesized in skeletal muscle following gene transfer with an adenovirus (Ad) or an AAV vector. In both cases, cellular immune responses resulted in the elimination of transduced muscle fibers within 4 weeks. However, the kinetics of CD4+ T-cell activation were markedly delayed when AAV vectors were used. Upon recombinant Ad (rAd) gene transfer, T cells were activated both by direct transduction of dendritic cells and by cross-presentation of the transgene product, while upon rAAV gene transfer T cells were only activated by the latter mechanism. These results suggested that activation of the immune system by the transgene product following rAAV-mediated gene transfer might be easier to control than that following rAd-mediated gene transfer. Therefore, we tested protocols aimed at interfering with either antigen presentation by blocking the CD40/CD40L pathway or with the T-cell response by inducing transgene-specific tolerance. Long-term expression of the AAV-HA was achieved in both cases, whereas immune responses against Ad-HA could not be prevented. These data clearly underline the importance of understanding the mechanisms by which vector-encoded proteins are recognized by the immune system in order to specifically interfere with them and to achieve safe and stable gene transfer in clinical trials.

scholarly journals Nutrition and immunity in the elderly

1999 ◽  
Vol 58 (3) ◽  
pp. 685-695 ◽  
Author(s):  
Bruno Lesourd ◽  
Lynda Mazari
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Elderly Population ◽  
The Elderly ◽  
Present Review ◽  
Cell Mediated Immunity ◽  
T Helper ◽  
Immune Changes

Immune function declines with age, leading to increased infection and cancer rates in aged individuals. In fact, recent progress in the study of immune ageing has introduced the idea that rather than a general decline in the functions of the immune system with age, immune ageing is mainly characterized by a progressive appearance of immune dysregulation throughout life. Changes appear earlier in life for cell-mediated immunity than for humoral immunity. Thus, agerelated modifications in cell-mediated immunity, i.e. changes in naive: memory T-cells, mature: immature T-cells, T-helper 1: T-helper 2 cells are more important in the elderly than changes in humoral immunity, i.e. CD5: CD5+ cells or length of antibody responses. Such evolution of the immune system has been linked to declining thymus function and to accumulative antigenic influence over the lifespan. In contrast, innate immunity (macrophage functions) is preserved or even increased during the ageing process. This finding shows that the ‘primitive’ immune system is less affected by the ageing process than the sophisticated specific immune system. The present review focuses on innate and cell-mediated immune changes with ageing. It provides evidence that primary changes (intrinsic modifications in the immune system) and secondary changes (resulting from environmental influences during the lifespan) exert different influences on the immune system. Primary changes, occurring in healthy individuals, seem less important nowadays than they were considered to be previously. For example, interleukin 2 secretion in some very healthy aged individuals is comparable with that in younger adults. Primary immune changes may not explain the increased incidence and severity of infections observed in the elderly population. Secondary immunological changes are far more frequent and are certainly responsible for most of the immune modifications observed in the elderly population. Environmental factors leading to secondary immune dysfunctions include not only antigenic influence, which is a reflection of diseases experienced over the lifespan, but also many other factors such as drug intake, physical activity and diet; factors for which important changes occur in the elderly population. Nutritional factors play a major role in the immune responses of aged individuals and the present review shows that nutritional influences on immune responses are of great consequence in aged individuals, even in the very healthy elderly.

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