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Responsible Editor | Enzyme Immunity Memory is an important immune mechanism for the body to resist the re-invasion of pathogens
.
The body produces heterogeneous memory CD8 T cells after the initial immune response, including effector memory T cells (TEM) circulating in blood tissues, central memory T cells (TCM) circulating in secondary lymphoid organs, and in tissues Tissue-resident T cells (TRM) that are long-resident
.
More and more evidences show that TRM plays a vital role in effectively fighting tissue area infections, but there are still many unsolved mysteries about the path of TRM cell generation in the initial immune response
.
Different from the traditional memory T cells that have experienced antigen-specific immune responses, there will also be a group of cells with memory cell characteristics in mice that have never experienced any immune response.
Previous studies have shown that they are produced by recognizing self-antigens.
, Is named Virtual Memory T Cell (TVM)
.
Under the stimulation of foreign antigens, TVM cells have different functional properties from naive T cells (TN) or true memory T cells, but whether there are subgroups with different functions in TVM cells and how TVM cells in a polyclonal state participate in tissue regional immunity It's not clear
.
On August 6, 2021, Science Immunology published an online research paper titled Virtual memory T-cells orchestrate extra-lymphoid responses conducive to resident memory by Professor Qi Hai’s research group from the Institute of Immunology of Tsinghua University
.
The study found that heterogeneous virtual memory T cells produced by the body recognizing its own antigens mediate a new mechanism of innate and acquired immune responses in regional tissue immune responses, providing new ideas for the design of CD8 T cell-based vaccines against lung infections
.
Using influenza virus to infect the lungs of SPF-free mice, the Qi Hai group researchers were surprised to find that a large number of TVM cells invaded the tissues as early as 18 hours after the infection, because the cells' tissue invasion depends on chemotaxis Factor receptors, through in vitro screening, researchers found that TVM cells have a subpopulation that expresses the chemokine receptor CCR2
.
And CCR2-positive TVM cells have a significant advantage in the early lung invasion process
.
Further explore the function of TVM cells invaded by these tissues through tools such as gene knockout mice and bone marrow reconstruction chimeric mice, and found that these cells have a very important function of controlling the viral load of the tissue in the early stage of virus infection.
It is mainly achieved through the non-specific innate immune characteristics of TVM cell antigens
.
In the traditional sense, the activation of T cells requires a complicated pathway: dendritic cells capture antigens and migrate to the local draining lymph nodes after the tissue is infected with pathogens, activate TN cells in the lymph nodes, and further differentiate into effector T cells and then migrate back to the regional tissues.
Play the effect function
.
However, due to a large number of TVM cells invading tissues in the early stage of infection, researchers speculated that this polyclonal cell population may have clonotypes that can directly recognize antigens in tissues, locally proliferate in the tissues and develop into antigen-specific effector cells
.
The researchers of the Qihai Group confirmed this hypothesis by using antibody blocking combined with single-cell sequencing methods.
They found that polyclonal TVM cells that invaded tissues in the early stage can proliferate antigen-specifically in a secondary lymphoid organ-independent manner, revealing a T cell.
A new way of activation
.
Finally, the researchers boldly speculated that the TVM cells that entered the tissues early might proliferate locally in the tissues and eventually develop into TRM cells.
.
Through polyclonal and monoclonal cell adoptive transfer experiments, Qi Hai group researchers found that TVM cells not only can, but also have a stronger ability to produce TRM cells.
This discovery reveals a new path for the generation of tissue-resident memory cells
.
Based on this, the researchers of the Qihai group discovered a new heterogeneous functional population of immune memory cells, revealing a new mechanism for the body to use TVM cells produced by autoimmunity to fight foreign pathogens.
TVM cells can be used as innate and acquired immunity.
Bridge, carry out immune inspections in the very early stage of immunity, carry out the specific elimination of pathogens in the effect phase, and develop TRM cells with stronger advantages than naive cells to fight the secondary immune response, providing new ideas for the design of cell vaccines
.
TVM cells participate in the primary immune response in non-lymphoid tissues and generate tissue-resident memory cells.
Professor Qi Hai’s research group focuses on the study of the regulation mechanism of humoral immune response, the molecular basis of the gender differences in immune response, and tissue-resident CD8 memory T Cell development mechanism and vaccine application, the regulation mechanism of central nervous circuit on immune response, etc.
, published many original papers on the cutting-edge scientific issues in the above fields in Nature, Science, Immunity, Nature Immunology and other journals
.
Dr.
Shiyue Hou from the School of Medicine of Tsinghua University and Tiange Shao, a 2015 doctoral student in the School of Medicine, are the co-first authors of this article.
The graduated Mao Tianyang, Dr.
Shi Jingwen, and 2018 doctoral student Jiahui Sun made important contributions
.
This project received important support from Professor Tan Xu and Dr.
Mei Miao from the School of Pharmacy of Tsinghua University
.
Original link: http://doi.
org/10.
1126/sciimmunol.
abg9433 Platemaker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting without permission is prohibited, and the author owns all the legal regulations.
Rights, offenders must be investigated
.
.
The body produces heterogeneous memory CD8 T cells after the initial immune response, including effector memory T cells (TEM) circulating in blood tissues, central memory T cells (TCM) circulating in secondary lymphoid organs, and in tissues Tissue-resident T cells (TRM) that are long-resident
.
More and more evidences show that TRM plays a vital role in effectively fighting tissue area infections, but there are still many unsolved mysteries about the path of TRM cell generation in the initial immune response
.
Different from the traditional memory T cells that have experienced antigen-specific immune responses, there will also be a group of cells with memory cell characteristics in mice that have never experienced any immune response.
Previous studies have shown that they are produced by recognizing self-antigens.
, Is named Virtual Memory T Cell (TVM)
.
Under the stimulation of foreign antigens, TVM cells have different functional properties from naive T cells (TN) or true memory T cells, but whether there are subgroups with different functions in TVM cells and how TVM cells in a polyclonal state participate in tissue regional immunity It's not clear
.
On August 6, 2021, Science Immunology published an online research paper titled Virtual memory T-cells orchestrate extra-lymphoid responses conducive to resident memory by Professor Qi Hai’s research group from the Institute of Immunology of Tsinghua University
.
The study found that heterogeneous virtual memory T cells produced by the body recognizing its own antigens mediate a new mechanism of innate and acquired immune responses in regional tissue immune responses, providing new ideas for the design of CD8 T cell-based vaccines against lung infections
.
Using influenza virus to infect the lungs of SPF-free mice, the Qi Hai group researchers were surprised to find that a large number of TVM cells invaded the tissues as early as 18 hours after the infection, because the cells' tissue invasion depends on chemotaxis Factor receptors, through in vitro screening, researchers found that TVM cells have a subpopulation that expresses the chemokine receptor CCR2
.
And CCR2-positive TVM cells have a significant advantage in the early lung invasion process
.
Further explore the function of TVM cells invaded by these tissues through tools such as gene knockout mice and bone marrow reconstruction chimeric mice, and found that these cells have a very important function of controlling the viral load of the tissue in the early stage of virus infection.
It is mainly achieved through the non-specific innate immune characteristics of TVM cell antigens
.
In the traditional sense, the activation of T cells requires a complicated pathway: dendritic cells capture antigens and migrate to the local draining lymph nodes after the tissue is infected with pathogens, activate TN cells in the lymph nodes, and further differentiate into effector T cells and then migrate back to the regional tissues.
Play the effect function
.
However, due to a large number of TVM cells invading tissues in the early stage of infection, researchers speculated that this polyclonal cell population may have clonotypes that can directly recognize antigens in tissues, locally proliferate in the tissues and develop into antigen-specific effector cells
.
The researchers of the Qihai Group confirmed this hypothesis by using antibody blocking combined with single-cell sequencing methods.
They found that polyclonal TVM cells that invaded tissues in the early stage can proliferate antigen-specifically in a secondary lymphoid organ-independent manner, revealing a T cell.
A new way of activation
.
Finally, the researchers boldly speculated that the TVM cells that entered the tissues early might proliferate locally in the tissues and eventually develop into TRM cells.
.
Through polyclonal and monoclonal cell adoptive transfer experiments, Qi Hai group researchers found that TVM cells not only can, but also have a stronger ability to produce TRM cells.
This discovery reveals a new path for the generation of tissue-resident memory cells
.
Based on this, the researchers of the Qihai group discovered a new heterogeneous functional population of immune memory cells, revealing a new mechanism for the body to use TVM cells produced by autoimmunity to fight foreign pathogens.
TVM cells can be used as innate and acquired immunity.
Bridge, carry out immune inspections in the very early stage of immunity, carry out the specific elimination of pathogens in the effect phase, and develop TRM cells with stronger advantages than naive cells to fight the secondary immune response, providing new ideas for the design of cell vaccines
.
TVM cells participate in the primary immune response in non-lymphoid tissues and generate tissue-resident memory cells.
Professor Qi Hai’s research group focuses on the study of the regulation mechanism of humoral immune response, the molecular basis of the gender differences in immune response, and tissue-resident CD8 memory T Cell development mechanism and vaccine application, the regulation mechanism of central nervous circuit on immune response, etc.
, published many original papers on the cutting-edge scientific issues in the above fields in Nature, Science, Immunity, Nature Immunology and other journals
.
Dr.
Shiyue Hou from the School of Medicine of Tsinghua University and Tiange Shao, a 2015 doctoral student in the School of Medicine, are the co-first authors of this article.
The graduated Mao Tianyang, Dr.
Shi Jingwen, and 2018 doctoral student Jiahui Sun made important contributions
.
This project received important support from Professor Tan Xu and Dr.
Mei Miao from the School of Pharmacy of Tsinghua University
.
Original link: http://doi.
org/10.
1126/sciimmunol.
abg9433 Platemaker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting without permission is prohibited, and the author owns all the legal regulations.
Rights, offenders must be investigated
.
