For the first time, the distribution and transport of CD8+ T cells in COVID-19 rehabilitation patients were revealed.

The study, published in Science Advances, provides new insights that could help better understand how the body's immune system responds to viral infections and develop long-term protection against reinfection.

The researchers used the uEXPLORER whole-body PET scanner, an innovative imaging technology developed at UC Davis in collaboration with United Medical Imaging.

Dynamic positron emission computed tomography involves injecting a very small amount of a radioactive tracer into the patient's body, followed by continuous imaging over a period of time. Dynamic positron emission computed tomography (PET) is an innovative technique developed by UC Davis in collaboration with United Medical Imaging. Mathematical models can then be applied to extract biologically relevant information.

For the first time, the distribution and transport of CD8+ T cells in COVID-19 rehabilitation patients were revealed.

Whole-body PET scanners provide simultaneous dynamic imaging and kinetic modeling of all organs in the body. They are significantly more sensitive than conventional PET systems. This means that lower doses of radiotracer can be used with better image quality.

This study is the first to use dynamic PET and kinetic modeling to measure the distribution of human CD8+ T cells, which are specific immune cells containing the CD8 protein on their surface. During a viral infection, naïve (non-customized) CD8+ T cells are activated and become cytotoxic. This means that they find and kill infected cells. Some of these CD8+ cells develop into antigen-specific memory T cells, which are used for long-term memory protection against reinfection.

These cells circulate in the bloodstream but are mainly found and function in non-blood tissues, especially lymphoid organs such as bone marrow, spleen, tonsils and lymph nodes.

The researchers recruited three healthy individuals and five patients who had recovered from COVID-19 infection. The recovered patients had mild or moderate symptoms and were not hospitalized.

The team injected the participants with a small amount of radioactive fluid, which included an immune PET radiotracer (8Zr-Df-Crefmirlimab) targeting human CD89. Ninety hours after the injection, the team performed a 60-minute dynamic scan, a 60-minute scan, and a 48-hour <> minute scan on each participant. Four months later, the recovered patients received the same scans.

The researchers measured the activity of the radiotracer in blood and non-blood tissues using PET images. They performed kinetic modeling to isolate the effects of blood circulation on the tissues. This allowed them to measure tissue uptake of the radiotracer independent of imaging time and differences in each participant's blood.

The results of the study showed that uptake of CD8+ T cells was high in the lymphoid organs of all participants. The spleen had the highest uptake, followed by bone marrow, liver, tonsils and lymph nodes.

The most important finding was an increase in the concentration of CD8+ T cells in the bone marrow of COVID-rehabilitated participants compared with healthy controls. On follow-up imaging (collected 6 months post-infection), CD8+ T cell concentrations in all bone marrow regions of the recovered patients were slightly higher than those collected approximately 2 months post-infection (baseline).

Bone marrow has been identified as the primary source and preferred site of proliferation of memory CD8+ T cells following viral infection. Delivery of memory T cells to specific tissues such as bone marrow is critical for the formation of immune memory following viral infection.

This study provides scientists with a new platform to study immune responses and memory in all organs in a non-invasive, long-term manner. It can be used to study immune responses during infection in cancer patients, immune memory after viral infection, and treatment response assessment. It can also be extended to the study of infectious diseases, autoimmune disorders and transplantation, and can be used for prognosis as well as therapy and vaccine development.

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