Human <scp>CD</scp>8 T‐cell activation in acute and chronic chikungunya infection

Dias, Cínthia Nóbrega de Sousa; Gois, Bruna Macêdo; Lima, Viviane Silva; Guerra-Gomes, Isabel Cristina; Araújo, Josélio Maria Galvão de; Gomes, Juliana de Assis Silva; Araújo, Demétrius Antônio Machado de; Medeiros, Isac A.; Azevedo, Fátima de Lourdes Assunção Araújo de; Veras, Robson Cavalcante; Janebro, Daniele Idalino; Amaral, Ian P.G.; Keesen, Tatjana Souza Lima

doi:10.1111/imm.12992

Cited by 17 publications

(22 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…T cell activation is typically observed during acute viral infections (58)(59)(60), and as expected (15,18) we observed increased activation of both CD4+ and CD8+ T cells in severe COVID-19 that correlated with the plasmablast frequency. However, T cell activation was very heterogeneous across the severe COVID-19 patients, being equivalent to baseline in some while reaching up to ~25% of memory CD8+ T cells in others.…”

Section: Modulation Of Innate Immune Cells Manifested In a Number Of supporting

confidence: 85%

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Kuri-Cervantes

Pampena

Meng

et al. 2020

Preprint

View full text Add to dashboard Cite

Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals.We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.One Sentence Summary: Broad immune perturbations in severe COVID-19 surrogates, as well as the medical personnel in charge of patient care.

show abstract

Section: Modulation Of Innate Immune Cells Manifested In a Number Of supporting

confidence: 85%

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Kuri-Cervantes

Pampena

Meng

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, the classical effector functions of CD8 ϩ T cells are not compromised during CHIKV infection, at least when analyzed ex vivo. These results are consistent with those of studies demonstrating that circulating CHIKV-specific CD8 ϩ T cells in patients with acute and chronic CHIKV disease also produce proinflammatory cytokines and exhibit cytolytic potential in response to ex vivo peptide restimulation (41,91). Similar observations were made using CD8 ϩ T cells from CHIKV-infected NHPs; however, as discussed above, the magnitude and breadth of the CHIKV-specific CD8 ϩ T cell responses are diminished in aged NHPs that develop persistent CHIKV infection (39).…”

Section: Discussionsupporting

confidence: 91%

Chikungunya Virus Evades Antiviral CD8⁺T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues

Davenport

Bullock

McCarthy

et al. 2020

J Virol

View full text Add to dashboard Cite

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes explosive epidemics of a febrile illness characterized by debilitating arthralgia and arthritis that can endure for months to years following infection. In mouse models, CHIKV persists in joint tissues for weeks to months and is associated with chronic synovitis. Using a recombinant CHIKV strain encoding a CD8+ T cell receptor epitope from ovalbumin, as well as a viral peptide-specific major histocompatibility complex class I tetramer, we interrogated CD8+ T cell responses during CHIKV infection. Epitope-specific CD8+ T cells, which were reduced in Batf3−/− and Wdfy4−/− mice with known defects in antigen cross-presentation, accumulated in joint tissue and the spleen. Antigen-specific ex vivo restimulation assays and in vivo killing assays demonstrated that CD8+ T cells produce cytokine and have cytolytic activity. Despite the induction of a virus-specific CD8+ T cell response, the CHIKV burden in joint-associated tissues and the spleen were equivalent in wild-type (WT) and CD8α−/− mice during both the acute and the chronic phases of infection. In comparison, CD8+ T cells were essential for the control of acute and chronic lymphocytic choriomeningitis virus infection in the joint and spleen. Moreover, adoptive transfer of virus-specific effector CD8+ T cells or immunization with a vaccine that induces virus-specific effector CD8+ T cells prior to infection enhanced the clearance of CHIKV infection in the spleen but had a minimal impact on CHIKV infection in the joint. Collectively, these data suggest that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part by evading CD8+ T cell immunity. IMPORTANCE CHIKV is a reemerging mosquito-transmitted virus that in the last decade has spread into Europe, Asia, the Pacific Region, and the Americas. Joint pain, swelling, and stiffness can endure for months to years after CHIKV infection, and epidemics have a severe economic impact. Elucidating the mechanisms by which CHIKV subverts antiviral immunity to establish and maintain a persistent infection may lead to the development of new therapeutic strategies against chronic CHIKV disease. In this study, we found that CHIKV establishes and maintains a persistent infection in joint-associated tissue in part by evading antiviral CD8+ T cell immunity. Thus, immunomodulatory therapies that improve CD8+ T cell immune surveillance and clearance of CHIKV infection could be a strategy for mitigating chronic CHIKV disease.

show abstract

“…Studies have reported that the peripheral blood of acute and chronic CHIKD patients had no differences in the percentage of CD8 + T cells in relation to healthy individuals. Analysis of early activation marker CD69 for CD8 + T cells revealed increased CD8 + T cell activation in both acute and chronic diseases (103). The study further observed that CD8 + T lymphocytes in patients with acute CHIKD have increased secretion of CD107A along with granzyme and perforin expression in comparison to the control group, suggesting that CD8 + T cells may have a role in mediating cytolytic killing of CHIKV infected cells during the acute phase of CHIKD (103).…”

Section: Immunopathology Of Acute Phasementioning

confidence: 67%

Disease Resolution in Chikungunya—What Decides the Outcome?

et al. 2020

View full text Add to dashboard Cite

Chikungunya disease (CHIKD) is a viral infection caused by an alphavirus, chikungunya virus (CHIKV), and triggers large outbreaks leading to epidemics. Despite the low mortality rate, it is a major public health concern owing to high morbidity in affected individuals. The complete spectrum of this disease can be divided into four phases based on its clinical presentation and immunopathology. When a susceptible individual is bitten by an infected mosquito, the bite triggers inflammatory responses attracting neutrophils and initiating a cascade of events, resulting in the entry of the virus into permissive cells. This phase is termed the pre-acute or the intrinsic incubation phase. The virus utilizes the cellular components of the innate immune system to enter into circulation and reach primary sites of infection such as the lymph nodes, spleen, and liver. Also, at this point, antigen-presenting cells (APCs) present the viral antigens to the T cells thereby activating and initiating adaptive immune responses. This phase is marked by the exhibition of clinical symptoms such as fever, rashes, arthralgia, and myalgia and is termed the acute phase of the disease. Viremia reaches its peak during this phase, thereby enhancing the antigen-specific host immune response. Simultaneously, T cell-mediated activation of B cells leads to the formation of CHIKV specific antibodies. Increase in titres of neutralizing IgG/IgM antibodies results in the clearance of virus from the bloodstream and marks the initiation of the post-acute phase. Immune responses mounted during this phase of the infection determine the degree of disease progression or its resolution. Some patients may progress to a chronic arthritic phase of the disease that may last from a few months to several years, owing to a compromised disease resolution. The present review discusses the immunopathology of CHIKD and the factors that dictate disease progression and its resolution.

show abstract

Human CD8 T‐cell activation in acute and chronic chikungunya infection

Cited by 17 publications

References 20 publications

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Chikungunya Virus Evades Antiviral CD8⁺T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues

Disease Resolution in Chikungunya—What Decides the Outcome?

Contact Info

Product

Resources

About

Human CD8 T‐cell activation in acute and chronic chikungunya infection

Cited by 17 publications

References 20 publications

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Chikungunya Virus Evades Antiviral CD8+T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues

Disease Resolution in Chikungunya—What Decides the Outcome?

Contact Info

Product

Resources

About

Chikungunya Virus Evades Antiviral CD8⁺T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues