T cell Responses in COVID-19

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Description: Watch our quick presentation to learn more about the importance of the T cell response during coronavirus infection. We also discuss a variety of BioLegend tools that help accelerate COVID-19 research, including multiplexing assays and antibodies for flow cytometry, proteogenomics, and western blotting.



Today we will look at a key part of the adaptive immune system’s anti-viral response: T cells. We’ll examine how T cells have been profiled in COVID-19 patients, and how BioLegend’s reagents could help accelerate research on SARS-CoV-2.

Adaptive T cell immunity plays a significant role in the defense against viruses. It consists of two major subpopulations, CD8 and CD4 positive T cells. Antigen Presenting Cells (also known as APCs) play a critical role in activation and differentiation of these T cells. APCs express MHC class I and II molecules that present self and non-self peptides to T cells via T cell receptors (TCRs).

T cells play a vital role in viral clearance, with CD8+ cytotoxic T cells capable of secreting an array of molecules such as perforin, granzymes, and IFN-γ to eradicate infected cells from the host. At the same time, CD4+ T helper cells can assist other cells of the immune system. For example they can enhance the ability of cytotoxic T cells and B cells to clear pathogens. However, persistent stimulation by the virus may induce T cell exhaustion, leading to the loss of cytokine production capability and reduced functionality.

Coronaviruses are a large family of enveloped RNA viruses that cause acute respiratory distress syndrome in people. 3 coronaviruses in the past 20 years caused the outbreaks called Severe Acute Respiratory Syndrome (SARS) in 2002, Middle East Respiratory Syndrome (MERS) in 2012 and COVID-19 in late 2019.

Studies on non-human primates and mice showed that both CD4 and CD8 T cell responses during SARS and MERS were important for the recognition and killing of virus infected cells, with CD8 T cell responses occurring more frequently and at a greater magnitude. Within CD4 T cell populations, the role of Th1 cells was established. They help to promote neutralizing antibody production from B cells. They also aid in cytokine production, including IFN-γ, TNF-α, and IL-2. Some of the T cells exposed to these viruses remain long-term in their host, allowing them to develop a memory response that sufficiently protected them from re-infection by the same virus.

While, it has been shown that T cell responses are necessary for resolving the viral infection in SARS and MERS, the role of T cells in COVID-19 patients hasn’t been established yet, but it is being studied.

T cell profiling HAS shown a reduction of peripheral CD4 and CD8 T cells in COVID-19 patients. This reduction includes the regulatory T cell population, which can promote immunosuppression. Both CD4 and CD8 T cell subsets exhibited exhausted phenotypes, as shown by the expression of markers like PD-1 and TIM-3. This trend was mostly seen among elderly patients over the age of 60 and in patients in the Intensive Care Unit. Overall, a decrease in T cell counts negatively correlated with patient survival.

Another study used single-cell RNA sequencing (scRNA-seq) and single-cell TCR-sequencing to comprehensively characterize cells from lung bronchoalveolar lavage fluid of COVID-19 patients. In contrast to peripheral blood, there was an observed increase of CD8 T cells, NK cells, and macrophages in lung tissues.

However, patients with severe cases have a lower proportion of CD8 T cells, and an increased proportion of macrophages, NK cells, and proliferating cells in comparison to mild patients. CD8 T cells have Been shown to express high levels of effector molecules, including Granzyme A, Granzyme K, FASLG, and CCL5.

As seen in panel A, the expansion levels in CD8 T cells were significantly higher in the mild disease group than the severe one. On average, more than 50% of the CD8 T cells in the mild group were expanded clones, which likely represented the SARS-CoV-2-specific T cells.

Panel B shows that single-cell TCR-sequencing in patients with mild symptoms exhibited higher CD8 T cell clonality in comparison to those with severe symptoms. This data, taken together with the expression of effector molecules previously discussed, indicates the importance of T cells in SARS-Cov-2 immunity.

So how can BioLegend products help with COVID-19 research?

Our Flow Cytometry and Western blot antibodies can help identify key intracellular signaling pathways involved in the T cell response.

BioLegend MojoSort™ Kits allow you to use magnetic nanoparticles to quickly isolate cells of interest such as CD8 and CD4 subsets with high purity and yield.

BioLegend Flex-T™ MHC Tetramers allow tracking of clonal T cell response against viral peptides when identifying potential vaccine candidates.

Our TotalSeq™ Reagents for Single-Cell Proteogenomics and TCR profiling will help reveal clonality, diversity, and antigen specificity of T cells with simultaneous measurement of cell surface protein expression. You can learn more about TotalSeq with our Proteogenomics eLearning materials, or visiting biolegend.com/totalseq

BioLegend offers a wide variety of products to characterize virus induced inflammation, cellular response, immune profiling and Biomarker screening.

Our ELISA and LEGENDplex Kits are trusted to accurately quantitate cytokine and chemokine levels.

In conclusion, preliminary studies have shown that the COVID-19 disease has an impact on T cell immunity, resulting in the reduction of peripheral CD4 and CD8 T cells and the local expansion of CD8 T cells in lung tissues. There is a correlation between CD8 + T cell clonal diversity and the severity of COVID-19 symptoms.

However, the T cell role and molecular mechanism of their function during this disease in healthy and immune compromised patients still needs further characterization.

As we have shown T cells are vital to COVID-19 immunity, we provide a number of tools to understand the cytokines they produce, their antigen specificity, and even their genetic content. If you have any questions about our reagents, please contact us here.

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