scholarly journals Gamma Delta T Cells and Their Involvement in COVID-19 Virus Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Georg von Massow ◽  
Steve Oh ◽  
Alan Lam ◽  
Kenth Gustafsson
Keyword(s):  
T Cells ◽  
Viral Infections ◽  
Cell Subset ◽  
Γδ T Cells ◽  
Common Symptom ◽  
Virus Infections ◽  
Infected Cells ◽  
The Relationship

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical αβ T cells. However, another subset of T cells called γδ T cells could have an important role to play. As part of the innate immune system, γδ T cells respond to inflammation and stressed or infected cells. The γδ T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because γδ T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for γδ T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cells in vitro. γδ T cells can take up, process and present antigens from microbes and human cells. As e.g. tumour-associated antigens are presented by MHC on γδ T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. γδ T cells are already used for medical purposes in oncology and have potential in cancer therapy. As γδ T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and γδ T cells.

scholarly journals Transcriptional role of p53 in interferon-mediated antiviral immunity

2008 ◽  
Vol 205 (8) ◽  
pp. 1929-1938 ◽  
Author(s):  
César Muñoz-Fontela ◽  
Salvador Macip ◽  
Luis Martínez-Sobrido ◽  
Lauren Brown ◽  
Joseph Ashour ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Viral Replication ◽  
Viral Infections ◽  
Suppressor Gene ◽  
Central Component ◽  
Type I ◽  
Infected Cells

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.

scholarly journals SARS-CoV-2-specific T cells in infection and vaccination

2021 ◽  
Vol 18 (10) ◽  
pp. 2307-2312 ◽  
Author(s):  
Antonio Bertoletti ◽  
Nina Le Bert ◽  
Martin Qui ◽  
Anthony T. Tan
Keyword(s):  
T Cells ◽  
Adaptive Immunity ◽  
Viral Infections ◽  
Infected Cells

AbstractDuring viral infections, antibodies and T cells act together to prevent pathogen spread and remove virus-infected cells. Virus-specific adaptive immunity can, however, also trigger pathological processes characterized by localized or systemic inflammatory events. The protective and/or pathological role of virus-specific T cells in SARS-CoV-2 infection has been the focus of many studies in COVID-19 patients and in vaccinated individuals. Here, we review the works that have elucidated the function of SARS-CoV-2-specific T cells in patients and in vaccinated individuals. Understanding whether SARS-CoV-2-specific T cells are more linked to protection or pathogenesis is pivotal to define future therapeutic and prophylactic strategies to manage the current pandemic.

scholarly journals A possible role of immunopathogenesis in COVID-19 progression

2020 ◽  
Author(s):  
Moritz Anft ◽  
Krystallenia Paniskaki ◽  
Arturo Blazquez-Navarro ◽  
Adrian Doevelaar ◽  
Felix S. Seibert ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Humoral Immunity ◽  
Viral Infections ◽  
Cell Subset ◽  
T Cell Response ◽  
T Cell Subsets ◽  
Clear Correlation

AbstractBackgroundThe efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities.MethodsIn this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity.ResultsSignificantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression.ConclusionOur data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.

scholarly journals Murine γδ T Lymphocytes Elicited duringPlasmodium yoelii Infection Respond to PlasmodiumHeat Shock Proteins

1999 ◽  
Vol 67 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Jeffrey Kopacz ◽  
Nirbhay Kumar
Keyword(s):  
T Cells ◽  
Γδ T Cells ◽  
Plasmodium Yoelii ◽  
Host Responses ◽  
Shock Proteins ◽  
Cellular Immune ◽  
Proliferation In Vitro

ABSTRACT γδ T cells accumulate during Plasmodium infections in both murine and human malarias. The biological role of these cells and the antigens that they recognize are not clearly understood, although recent findings indicate that γδ T cells in general influence both innate and antigen-specific adaptive host responses. We examined the accumulation of γδ T cells elicited during infection with virulent and avirulent Plasmodium yoelii parasites in relatively susceptible and resistant strains of mice. Our results indicated that in nonlethal malaria infections, γδ T cells comprise a larger proportion of splenic T cells than in lethal infections and that only a live infection is capable of inducing an increase in the percentage of γδ T cells in vivo. Furthermore, we demonstrate that γδ T cells elicited during a P. yoelii infection respond by proliferation in vitro to P. falciparum heat shock proteins (HSPs) of 60 and 70 kDa, suggesting a possible immunological involvement of parasite HSPs in this arm of the cellular immune response during malarial infection in mice.

scholarly journals Shared reactivity of Vδ2neg γδ T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells

2005 ◽  
Vol 201 (10) ◽  
pp. 1567-1578 ◽  
Author(s):  
Franck Halary ◽  
Vincent Pitard ◽  
Dorota Dlubek ◽  
Roman Krzysiek ◽  
Henri de la Salle ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Γδ T Cells ◽  
Γδ T Cell ◽  
Kidney Transplant Recipients ◽  
T Cell Clones ◽  
Cell Clones ◽  
Infected Cells

Long-lasting expansion of Vδ2neg γδ T cells is a hallmark of cytomegalovirus (CMV) infection in kidney transplant recipients. The ligands of these cells and their role remain elusive. To better understand their immune function, we generated γδ T cell clones from several transplanted patients. Numerous patient Vδ1+, Vδ3+, and Vδ5+ γδ T cell clones expressing diverse Vγ chains, but not control Vγ9Vδ2+ T clones, displayed strong reactivity against CMV-infected cells, as shown by their production of tumor necrosis factor-α. Vδ2neg γδ T lymphocytes could also kill CMV-infected targets and limit CMV propagation in vitro. Their anti-CMV reactivity was specific for this virus among herpesviridae and required T cell receptor engagement, but did not involve major histocompatibility complex class I molecules or NKG2D. Vδ2neg γδ T lymphocytes expressed receptors essential for intestinal homing and were strongly activated by intestinal tumor, but not normal, epithelial cell lines. High frequencies of CMV- and tumor-specific Vδ2neg γδ T lymphocytes were found among patients' γδ T cells. In conclusion, Vδ2neg γδ T cells may play a role in protecting against CMV and tumors, probably through mucosal surveillance of cellular stress, and represent a population that is largely functionally distinct from Vγ9Vδ2+ T cells.

Role of regulatory T-cells in autoimmunity

2009 ◽  
Vol 116 (8) ◽  
pp. 639-649 ◽  
Author(s):  
Richard J. Mellanby ◽  
David C. Thomas ◽  
Jonathan Lamb
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Treg Cell ◽  
Cell Function ◽  
Cell Subset ◽  
Treg Cells ◽  
Self Tolerance

There has been considerable historical interest in the concept of a specialist T-cell subset which suppresses over-zealous or inappropriate T-cell responses. However, it was not until the discovery that CD4+CD25+ T-cells had suppressive capabilities both in vitro and in vivo that this concept regained credibility and developed into one of the most active research areas in immunology today. The notion that in healthy individuals there is a subset of Treg-cells (regulatory T-cells) involved in ‘policing’ the immune system has led to the intensive exploration of the role of this subset in disease resulting in a number of studies concluding that a quantitative or qualitative decline in Treg-cells is an important part of the breakdown in self-tolerance leading to the development of autoimmune diseases. Although Treg-cells have subsequently been widely postulated to represent a potential immunotherapy option for patients with autoimmune disease, several studies of autoimmune disorders have demonstrated high numbers of Treg-cells in inflamed tissue. The present review highlights the need to consider a range of other factors which may be impairing Treg-cell function when considering the mechanisms involved in the breakdown of self-tolerance rather than focussing on intrinsic Treg-cell factors.

Antibody-dependent anti-cytomegalovirus activity of human γδ T cells expressing CD16 (FcγRIIIa)

Blood ◽  
2012 ◽  
Vol 119 (6) ◽  
pp. 1418-1427 ◽  
Author(s):  
Lionel Couzi ◽  
Vincent Pitard ◽  
Xavier Sicard ◽  
Isabelle Garrigue ◽  
Omar Hawchar ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hcmv Infection ◽  
Γδ T Cells ◽  
Cell Receptor ◽  
T Cell Response ◽  
Transplant Recipients ◽  
Antiviral Function ◽  
Infected Cells

Abstract Human cytomegalovirus (HCMV) infection is an important cause of morbidity and mortality in transplant recipients. Long-term protective immunity against HCMV requires both sustained specific T-cell response and neutralizing IgG production, but the interplay between these effector arms remains poorly defined. We previously demonstrated that γδ T cells play a substantial role as anti-HCMV T-cell effectors. The observation that CD16 (FcγRIIIA) was specifically expressed by the majority of HCMV-induced γδ T cells prompted us to investigate their cooperation with anti-HCMV IgG. We found that CD16 could stimulate γδ T cells independently of T-cell receptor (TCR) engagement and provide them with an intrinsic antibody-dependent cell-mediated cytotoxic (ADCC) potential. Although CD16+γδ T cells did not mediate ADCC against HCMV-infected cells, in accordance with the low level of anti-HCMV IgGs recognizing infected cells, they produced IFNγ when incubated with IgG-opsonized virions. This CD16-induced IFNγ production was greatly enhanced by IL12 and IFNα, 2 cytokines produced during HCMV infection, and conferred to γδ T cells the ability to inhibit HCMV multiplication in vitro. Taken together, these data identify a new antiviral function for γδ T cells through cooperation with anti-HCMV IgG that could contribute to surveillance of HCMV reactivation in transplant recipients.

scholarly journals Immune Checkpoints in Viral Infections

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1051
Author(s):  
Huiming Cai ◽  
Ge Liu ◽  
Jianfeng Zhong ◽  
Kai Zheng ◽  
Haitao Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cancer Cells ◽  
Antiviral Therapy ◽  
Immune Checkpoint ◽  
Viral Infections ◽  
Immune Checkpoints ◽  
Chronic Viral Infections ◽  
Infected Cells

As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.

scholarly journals Cryopreservation of Whole Tumor Biopsies from Rectal Cancer Patients Enable Phenotypic and In Vitro Functional Evaluation of Tumor-Infiltrating T Cells

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2428
Author(s):  
Frank Liang ◽  
Azar Rezapour ◽  
Peter Falk ◽  
Eva Angenete ◽  
Ulf Yrlid
Keyword(s):  
Rectal Cancer ◽  
T Cells ◽  
Γδ T Cells ◽  
T Cell Subsets ◽  
Functional Evaluation ◽  
Mait Cells ◽  
Ifn Γ ◽  
Tumor Biopsies

TILs comprise functionally distinct conventional and unconventional T cell subsets and their role in responses to CRC treatments is poorly understood. We explored recovery of viable TILs from cryopreserved tumor biopsies of (chemo)-radiated patients with rectal cancer to establish a platform for retrospective TIL analyses of frozen tumors from pre-selected study cohorts. Frequencies of TIL subsets and their capacity to mount IFN-γ responses in cell suspensions of fresh vs. cryopreserved portions of the same tumor biopsies were determined for platform validation. The percentages and proportions of CD4+ TILs and CD8+ cytotoxic T lymphocytes (CTLs) among total TILs were not affected by cryopreservation. While recovery of unconventional γδ T cells and mucosal-associated invariant T cells (MAIT cells) was stable after cryopreservation, the regulatory T cells (Tregs) were reduced, but in sufficient yields for quantification. IFN-γ production by in vitro-stimulated CD4+ TILs, CTLs, γδ T cells, and MAIT cells were proportionally similar in fresh and cryopreserved tumor portions, albeit the latter displayed lower levels. Thus, the proposed platform intended for TIL analyses on cryopreserved tumor biobank biopsies holds promises for studies linking the quantity and quality of TIL subsets with specific clinical outcome after CRC treatment.

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