Standard tests to assess T cells may unravel Covid-19 mysteries: Scientists

Since immunity against the novel coronavirus is contributed by both the antibodies and cells of the immune system, simpler, standardised lab tests to assess the T cell response in Covid-19 patients may help unravel more mysteries about the disease, say scientists.

Immunologist Satyajit Rath noted that the two major components of immunity specific for any infection are the T cell responses, and those mediated by the immune system's B cells along with the antibody proteins they produce.

"Antibody responses are easier to measure, especially on a large scale, and they have traditionally been the protective components of vaccine-induced immunity. Therefore, they always tend to be focused upon, as is true in the ongoing pandemic as well," Rath, from the National Institute of Immunology (NII) in New Delhi, told PTI.

T cell responses, he added, while also "very important," are "technically much harder to study, particularly in human communities."

According to Rath, a subset CD8 T cells provide a major anti-viral immune function which may have a substantive role to play, especially in people whose antibody responses turn out to be short-lived.

Daniel Altmann, Professor of Immunology at the University College London in the UK, agreed with Rath.

"One of the best indicators of the importance of T cell immunity comes from reports of people who have made full recovery from COVID-19 despite the complete absence of antibodies," he told PTI.

Another subset of the T cells -- called CD4 T cells -- help the B cell-antibody response become more efficient and long-lived, Rath noted, adding that these must be examined in order to understand the efficiency and longevity of antibody responses.

According to the NII immunologist, CD4 T cell responses also contribute anti-viral functions as well as causing tissue and organ damage.

"So, CD8 T cell responses can kill virus-infected cells of the body and limit virus growth. But in the process, a lot of cells of the body end up dead, and this can lead to organs being unable to function well, and hence illness. CD4 T cell responses, too, can and do cause inflammation," Rath said.

Virologist Upasana Ray also noted that both T cell immunity and antibodies are important.

She said while a subset of T cells, called cytotoxic T cells, help in eliminating virus infected cells, antibodies are key chemical mediators in neutralising the virus entry process into cells.

"Since we are more equipped with antibody testing, it is desirable to have reliable T cell testing kits. This might also help to monitor T cell subsets that have different functions in immune system," Ray, Senior Scientist at the CSIR-Indian Institute of Chemical Biology told PTI.

Altmann added that T cell analysis may reveal how long-term Covid-19 immunity is generated.

"It's looking clearer that while antibodies are important, the tests are rather transient as their levels wane very fast. By contrast, T cell testing may offer an answer decades from infection," he expalined.

Ray emphasised that one of the important reasons to study T cells is their depletion observed in severe Covid-19 cases.

For instance, a recent study published in the journal Cell assessed blood samples of 17 acute and 24 recovered Covid-19 patients, and found that severe infection with the virus resulted in a reduction of T cell count, as well as their function.

"Covid-19 has been associated with both reduction as well as functional exhaustion of T cells," Ray said, adding that their lowered levels could be in parallel with the severity of the disease.

Based on published studies, Ray said, markers for the exhaustion of T cells such as the molecules PD-1 and Tim-3 can be detected more in severe Covid-19 cases.

"More of such studies in non-severe, severe, and recovered individuals might help to understand the complex regulatory framework of T cell number and function correlations. This might also open novel directions for targeting this disease based on T cell biology," she said.

According to Ray, studies analysing the complexity of T cells in Covid-19 patients, and targeting T cell exhaustion pathways can provide valuable insights about the disease.

"We need to know the magnitudes of CD4 and CD8 T cell responses separately. We need to know the viral targets of these T cells. We need to know the associations of these various parameters with the extent and kinds of illness. We need to know how these T cell responses behave over time," Rath added.

While both antibody and T cell-mediated immunity are important, Ray said researchers are more equipped with antibody testing than for T cells.

Immunologist A R Anand from the Vision Research Foundation in Chennai said the estimation of T cell immune response is much more difficult than determining neutralising antibody levels.

"T cell response, in general, is difficult to study. Most of the widely available tests only seem to say whether there has been T cell activation or not. But we need to know how many virus-specific T cells are there, which is tricky to measure," he told PTI.

Rath agreed that there is a need to develop standardised tests to assess the T cell response in Covid-19 patients across the severity spectrum. While some existing kits have been developed for evaluating the CD4 T cell response to bacterial infections, he said Covid-19 may need assessment of CD8 T cell as well.

"These may be more difficult to develop as commercial tests. So multiple tests may well be needed, and they will all need much validation," Rath added.