Role of the cellular immunity in the formation of the immune response in coronavirus infections

The data obtained during previous epidemics caused by coronaviruses, and current pandemic indicate that assessing the role of certain immune interactions between these viruses and the microorganism is the main pre-requisite for development of diagnostic test systems as well as effective medical drugs and preventive measures. The review summarizes the results of studying patho– and immunogenesis of SARSCoV, MERS-CoV, and SARS-CoV-2 infections. These coronaviruses were proven to suppress development of adaptive immune response at the stage of its induction, affecting the number and functional activity of lymphocytes, effectors of cellular immunity, causing impairment of lymphopoiesis, apoptosis and «depletion» of these cells, thus leading to longer duration of the disease and increased viral load. Information about the role of cellular immunity in development of immune response to coronaviruses is presented. It was proven that the causative agents of SARS, MERS and COVID-19 trigger adaptive immune response in the microorganism according to both humoral and cellular types. Moreover, the synthesis of specific immunoglobulins does not yet point to presence of protective immune response. Activation of the cellular link of immunity is also important. A high degree of antigenic epitope homology in SARS-CoV, MERS-CoV and SARS-CoV-2 is described, thus suggesting an opportunity for cross-immunity to coronaviruses. The review addresses issues related to the terms of specific memory immune cells to SARS-CoV, MERS-CoV and SARS-CoV-2, and their role in providing long-term protection against these infections. Given that specific antibodies to SARS and MERS pathogens persisted for a year, were often not detected or briefly registered in patients with mild and asymptomatic infections, we can talk about important role of the cellular immune response in providing immunity to these coronaviruses. It was shown that, in contrast to antibodies, the antigen-specific memory T cells were registered in patients with SARS virus for 4 to 11 years, and Middle East Respiratory Syndrome – up to two years. Further research is needed to determine presence and number of memory T cells in COVID-19. A comparative analysis of data obtained during previous epidemics with respect to formation of adaptive immunity to coronaviruses. Description of proteins and epitopes recognized by human T lymphocytes will be useful in monitoring immune responses in COVID-19 patients, as well as in developing informative tests to study T cell immune response to SARS-CoV-2 and new preventive drugs.

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Activation of NKT Cells Protects Mice from Tuberculosis

Infection and Immunity ◽

10.1128/iai.70.11.6302-6309.2002 ◽

2002 ◽

Vol 70 (11) ◽

pp. 6302-6309 ◽

Cited By ~ 135

Author(s):

Alissa Chackerian ◽

Jen Alt ◽

Vaji Perera ◽

Samuel M. Behar

Keyword(s):

Immune Response ◽

T Cells ◽

Tissue Injury ◽

Adaptive Immune Response ◽

Nkt Cells ◽

Cell Immune Response ◽

Class I Mhc ◽

Mhc I ◽

Mhc Ii

ABSTRACT The T-cell immune response to Mycobacterium tuberculosis is critical in preventing clinical disease. While it is generally accepted that both major histocompatibility complex class I (MHC-I)-restricted CD8+ and MHC-II-restricted CD4+ T cells are important for the immune response to M. tuberculosis, the role of non-MHC-restricted T cells is still not clearly delineated. We have previously reported that CD1d−/− mice do not differ from CD1d+/+ mice in their survival following infection with M. tuberculosis. We now show that, although CD1d-restricted NKT cells are not required for optimum immunity to M. tuberculosis, specific activation of NKT cells by the CD1d ligand α-galactosylceramide protects susceptible mice from tuberculosis. Treatment with α-galactosylceramide reduced the bacterial burden in the lungs, diminished tissue injury, and prolonged survival of mice following inoculation with virulent M. tuberculosis. The capacity of activated NKT cells to stimulate innate immunity and modulate the adaptive immune response to promote a potent antimicrobial immune response suggests that α-galactosylceramide administration could have a role in new strategies for the therapy of infectious diseases.

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Revealing the role of CD4+ T cells in viral immunity

Journal of Experimental Medicine ◽

10.1084/jem.20121517 ◽

2012 ◽

Vol 209 (8) ◽

pp. 1391-1395 ◽

Cited By ~ 101

Author(s):

Andrea J. Sant ◽

Andrew McMichael

Keyword(s):

Immune Response ◽

T Cells ◽

Cd4 T Cells ◽

Adaptive Immune Response ◽

Neutralizing Antibody ◽

Viral Immunity ◽

Antigen Specificity ◽

Viral Pathogens ◽

Adaptive Immune

Protective immunity to chronic and acute viral infection relies on both the innate and adaptive immune response. Although neutralizing antibody production by B cells and cytotoxic activity of CD8+ T cells are well-accepted components of the adaptive immune response to viruses, identification of the specific role of CD4+ T cells in protection has been more challenging to establish. Delineating the contribution of CD4+ T cells has been complicated by their functional heterogeneity, breadth in antigen specificity, transient appearance in circulation, and sequestration in tissue sites of infection. In this minireview, we discuss recent progress in identifying the multiple roles of CD4+ T cells in orchestrating and mediating the immune responses against viral pathogens. We highlight several recent reports, including one published in this issue, that have employed comprehensive and sophisticated approaches to provide new evidence for CD4+ T cells as direct effectors in antiviral immunity.

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Persistent cellular immunity to SARS-CoV-2 infection

Journal of Experimental Medicine ◽

10.1084/jem.20202515 ◽

2021 ◽

Vol 218 (4) ◽

Author(s):

Gaëlle Breton ◽

Pilar Mendoza ◽

Thomas Hägglöf ◽

Thiago Y. Oliveira ◽

Dennis Schaefer-Babajew ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Cell Division ◽

T Cell ◽

Cellular Immunity ◽

Memory T Cells ◽

Cell Responses ◽

Paired Samples ◽

Specific Memory ◽

Cd8 Memory T Cells

SARS-CoV-2 is responsible for an ongoing pandemic that has affected millions of individuals around the globe. To gain further understanding of the immune response in recovered individuals, we measured T cell responses in paired samples obtained an average of 1.3 and 6.1 mo after infection from 41 individuals. The data indicate that recovered individuals show persistent polyfunctional SARS-CoV-2 antigen–specific memory that could contribute to rapid recall responses. Recovered individuals also show enduring alterations in relative overall numbers of CD4+ and CD8+ memory T cells, including expression of activation/exhaustion markers, and cell division.

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Regulating the Adaptive Immune Response to Blood-Stage Malaria: Role of Dendritic Cells and CD4+Foxp3+ Regulatory T Cells

International Journal of Biological Sciences ◽

10.7150/ijbs.7.1311 ◽

2011 ◽

Vol 7 (9) ◽

pp. 1311-1322 ◽

Cited By ~ 23

Author(s):

Mary M. Stevenson ◽

Rebecca Ing ◽

Floriana Berretta ◽

Jenny Miu

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Regulatory T Cells ◽

Adaptive Immune Response ◽

Blood Stage ◽

Adaptive Immune ◽

Blood Stage Malaria

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CD8+γδ T Cells Are More Frequent in CMV Seropositive Bone Marrow Grafts and Display Phenotype of an Adaptive Immune Response

Stem Cells International ◽

10.1155/2019/6348060 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Ahmed Gaballa ◽

Lucas C. M. Arruda ◽

Emelie Rådestad ◽

Michael Uhlin

Keyword(s):

Bone Marrow ◽

Immune Response ◽

T Cells ◽

T Cell ◽

Gene Segment ◽

Adaptive Immune Response ◽

T Cell Subsets ◽

Effector Memory ◽

Adaptive Immune

The role of gamma delta (γδ) T cells in human cytomegalovirus (HCMV) immune surveillance has been the focus of research interest for years. Recent reports have shown a substantial clonal proliferation of γδ T cells in response to HCMV, shedding light on the adaptive immune response of γδ T cells. Nevertheless, most efforts have focused on Vδ2negγδ T cell subset while less attention has been given to investigate other less common γδ T cell subsets. In this regard, a distinct subpopulation of γδ T cells that expresses the CD8 coreceptor (CD8+γδ T cells) has not been thoroughly explored. Whether it is implicated in HCMV response and its ability to generate adaptive response has not been thoroughly investigated. In this study, we combined flow cytometry and immune sequencing of the TCR γ-chain (TRG) to analyze in-depth bone marrow (BM) graft γδ T cells from CMV seropositive (CMV+) and CMV seronegative (CMV-) donors. We showed that the frequency of CD8+γδ T cells was significantly higher in CMV+ grafts compared to CMV- grafts (P<0.001). Further characterization revealed that CD8+γδ T cells from CMV+ grafts express Vγ9- and preferentially differentiated from a naive to terminal effector memory phenotype (CD27low/-CD45RO-). In line with these findings, TRG immune sequencing revealed clonal focusing and reduced usage of the Vγ9/JP gene segment in a CMV+ graft. Furthermore, CD8+γδ T cells showed an enhanced response to TCR/CD3 and cytokine stimulation in contrast to CD8-γδ T cells. We conclude that γδ T cells in BM grafts are reshaped by donor CMV serostatus and highlight the potential adaptive role of CD8+γδ T cells in HCMV immune response.

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Adaptive Immunity: The Role of Toll-Like Receptors

Austin Journal of Allergy ◽

10.26420/austinjallergy.2021.1038 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yamaguchi R ◽

◽

Sakamoto A ◽

Yamaguchi R ◽

Haraguchi M ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Autoimmune Diseases ◽

Adaptive Immunity ◽

Th17 Cells ◽

Adaptive Immune Response ◽

Toll Like Receptors ◽

Adaptive Immune ◽

Interleukin 23

The central mediators of the adaptive immune response are T cells. The clonal expansion of T cells required for adaptive immunity results from the innate immune response, which is triggered by the stimulation of Toll-Like Receptors (TLRs). The adaptive immune response can cause autoimmune diseases, and Th17 cells are known to contribute to several autoimmune diseases. Pathogenic Th17 cells are induced by Interleukin 23 (IL-23) and IL-1Β. Resiquimod (a TLR7/8 agonist) significantly enhances IL-23 production by human macrophages, and lipopolysaccharide (a TLR4 agonist) slightly enhances it. Interestingly, IL-23 levels are significantly attenuated after sequential stimulation with lipopolysaccharide and resiquimod, indicating cross-talk between the TLR4 and TLR7/8 signaling pathways. In this review, we discuss the pivotal role of TLRs in triggering innate immunity and inducing adaptive immunity, leading to autoimmune diseases.

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