T cells play an important role in the human immune system. The blood cells
classified as lymphocytes are formed in the bone marrow. From there they
travel through blood vessels to the thymus gland in the breastbone. They
then form receptors on their cellular surface to identify and fight foreign
matter. The T cells also stimulate the formation of B cells, which produce
antibodies to attack viruses. Virus-specific immune responses by T cells can
be detected in the blood months or even years after an infection.
In view of the millions of people infected by Covid-19 and the emerging
fourth wave of the pandemic, it is of great interest to learn more about the
T cells that fight the virus. The T cells are enormously important for
protecting against a SARS-CoV-2 infection or preventing serious illness.
“We’re especially interested in how many of these specific T cells are
present in the body of an infected person, the qualities that enable these
cells to respond to the virus, and how long the T cells last,” says Dr.
Kilian Schober of the TUM Institute for Medical Microbiology, Immunology and
Hygiene.
Identifying the T cells that fight SARS-CoV-2
An interdisciplinary team of researchers at TUM, Helmholtz Zentrum München
and LMU Munich has now succeeded in developing a method for finding the T
cell receptors that respond to SARS-CoV-2. The team divided blood samples
taken from seriously infected Covid-19 patients into two pools. The samples
in the first pool were then stimulated with the virus antigen, with the
second pool left untreated. “This enabled us to identify the T cells that
responded to the virus and characterize a precise phenotype,” says Dr.
Herbert Schiller, group leader at Helmholtz Zentrum München. “So we now have
a profile to identify a T cell that fights SARS-CoV-2.”
T cells show whether the infection is still active
The Munich researchers now know what T cells look like that have recently
been exposed to the virus-fighting antigen. Similar T cells were found not
only in the blood, but also in the respiratory tract of patients. This made
it possible to distinguish between cells still in the “hot phase” and those
that have become dormant (“cold”) – in other words, whether a patient is
still fighting the infection or has already overcome it.
The results of the study are highly significant. They enable us to
distinguish between SARS-CoV-2-specific T cells in different organs (blood
or lungs), different activation states (antigen seen recently or not) and in
different illness contexts (seriously ill/virus positive or mildly ill/virus
negative). “We now have a better understanding of the appearance of T cells
targeting SARS-CoV-2 and how numerous they are in the blood and respiratory
tract,” says Prof. Dirk Busch, the Director of the TUM Institute for Medical
Microbiology, Immunology and Hygiene. “In the future, this process can
probably also be used to determine how many protective T cells are present
after a vaccination.”
Providing T cells with receptors to save seriously ill patients
The team working with lab director Prof. Dirk Busch also succeeded in
modifying T cells of healthy individuals to enable a first response to
SARS-CoV-2. “That shows that it might be possible to equip the T cells of
patients with receptors to fight the virus more effectively,” says Kilian
Schober. This is the first step towards an adoptive T cell treatment for
seriously ill Covid-19 patients. The process may also be applicable to other
diseases through better characterization of T cell responses – an important
hope for treatments of autoimmune conditions and cancers.
Reference:
Fischer DS, Ansari M, Wagner KI, et al. Single-cell RNA sequencing reveals
ex vivo signatures of SARS-CoV-2-reactive T cells through ‘reverse
phenotyping.’ Nat Commun. 2021;12(1):4515.
doi:10.1038/s41467-021-24730-4