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Editor | xi Immune memory is one of the important mechanisms used by the adaptive immune system of organisms to resist the re-invasion of pathogens
.
Compared with the initial T cells, memory T cells can react faster and more intensely after encountering the same antigen to effectively control the process of infection or disease.
This is also one of the important basic mechanisms of current vaccines
.
Recent studies have shown that memory T cells are highly heterogeneous and consist of cell subgroups with different cyclic migration, function and lifespan characteristics (Jameson and Masopust, 2018)
.
From the perspective of circulatory migration, memory T cells can be divided into circulating cells and resident cells: circulating cells include central memory T cells (Tcm) and effector memory T cells (Tem), which can pass through blood and lymph in various tissues and organs of the body Circulate continuously; correspondingly, tissue-resident memory T cells (Trm) reside in non-lymphoid tissues under normal physiological conditions and do not exchange with circulating cells in the blood
.
Due to its special location advantages, Trm can play the first-line rapid barrier protection function against the infection of bacteria or tumors in the tissues where it resides (Masopust and Soerens, 2019)
.
Therefore, the research on regulating the differentiation and maintenance of Trm fate has considerable significance
.
T cell co-stimulatory molecule (Co-stimulatory molecule) signals can affect the differentiation and fate selection of initial T cells together with T cell receptors (TCR) and cytokines in the environment
.
Although there are many substantive research advances on cytokines and transcription factors that promote Trm production, whether there are specific costimulatory molecules and whether the interaction between cells in non-lymphoid tissues can induce the differentiation of the tissue-resident population Still unknown
.
In response to this issue, on December 20, 2021, the University of Minnesota Stephen Jameson's laboratory (the first author is PhD student Peng Changwei) published a titled Engagement of ICOS in tissues promotes establishment of CD8+ tissue-resident memory in Immunity.
The research article of T cells revealed that in the mouse acute infection model, the inducible costimulatory molecule ICOS can specifically mediate the efficient maturation and differentiation of CD8+ tissue-resident memory T cells in non-lymphoid tissues
.
The inducible costimulatory molecule ICOS has a clear role in the differentiation of CD4+ helper T cells, and it is essential for the differentiation of follicular helper cells (Tfh) in the germinal center response
.
However, the role of ICOS in the differentiation of CD8+ cytotoxic T cells remains unclear
.
First, through different acute infection models of viruses or bacteria, the researchers found that the number of CD8+ T cells deficient in ICOS was no different in the peripheral circulating memory T cells compared with the wild type.
However, the number of CD8+ T cells in non-lymphoid tissues However, the memory-retaining cells showed a significant lack of specificity
.
This finding is mutually corroborated by the high expression of the ICOS gene as a CD8+ resident cell in the previous report
.
Through the study of different time points after infection, it is further found that the absence or blocking of ICOS does not affect the initial activation of CD8+ T cells or the expansion of effector cells, and it can migrate to non-lymphatic tissues as effectively as wild-type at the initial stage of infection.
However, defects appear in the process of further differentiation and maturation in the subsequent tissues
.
In contrast, blocking the ICOS signal of mature CD8+ resident memory cells will not affect their long-term maintenance
.
In order to further determine the time and mechanism of the effect of ICOS on CD8+ resident memory cells, the researchers used adoptive transfer to show whether CD8+ T cells were co-stimulated by ICOS during the activation and proliferation stage in the lymphatic tissues at the initial stage of infection.
The signal has no effect on the subsequent maturation and differentiation into Trm in normal non-lymphoid tissues; on the contrary, adoptive transfer of CD8+ effector T cells that normally receive ICOS costimulatory signals into ICOS-L-deficient mice will have no effect on them.
The differentiation of Trm in lymphoid tissues is hindered
.
Since the ligand ICOS-L of ICOS is widely expressed in various antigen-presenting cells and stromal cells and epithelial cells of non-lymphoid tissues, it is difficult to determine the source of the ICOS costimulatory signal that mediates CD8+ Trm
.
Researchers through bone marrow chimera studies have shown that: unlike CD4+ Tfh, which uses B cells in lymphoid organs as the source of ICOS-L, the ICOS-L costimulatory signal of CD8+ Trm originates from non-lymphatic tissues that do not respond to radiation.
Sensitive cell populations-including cell populations derived from non-hematopoietic stem cells or antigen-presenting cells residing in tissues
.
Finally, through single-cell sequencing to compare wild-type and ICOS-deficient CD8+ T cells in the early stage of infection and mature memory stage, the researchers proved from the transcriptome that the CD8+ tissue-resident cells lacking ICOS are very different from wild-type CD8+ T cells.
Small
.
This reflects that ICOS, as a costimulatory signal in the tissue, mainly mediates the efficiency of the differentiation and maturation of CD8+ resident cells without affecting its quality
.
Further molecular mechanism studies have shown that the PI3K signal mediated by ICOS and its downstream transcription factor KLF2 play an important role in the tissue residence of CD8+ T cells
.
In summary, this study shows the role of the classical costimulatory molecule ICOS in the differentiation of CD8+ T lymphocytes-it can specifically and efficiently induce the production of resident memory cells in the tissue without affecting peripheral circulating memory cells
.
In addition, ICOS costimulatory signals mainly act after CD8+ T lymphocytes migrate to non-lymphoid tissues, and are mediated by local radiation-insensitive cell populations.
This is the role of the tissue microenvironment in the differentiation and maturation of tissue resident memory cells New avenues have been opened up
.
Due to the effectiveness of tissue-resident memory cells for vaccines and their high similarity with tumor infiltrating cells, the target of ICOS/ICOS-L costimulatory signals can become a new idea for the treatment of related diseases
.
Original link: https://doi.
org/10.
1016/j.
immuni.
2021.
11.
017 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights , The offender must be investigated
.
.
Compared with the initial T cells, memory T cells can react faster and more intensely after encountering the same antigen to effectively control the process of infection or disease.
This is also one of the important basic mechanisms of current vaccines
.
Recent studies have shown that memory T cells are highly heterogeneous and consist of cell subgroups with different cyclic migration, function and lifespan characteristics (Jameson and Masopust, 2018)
.
From the perspective of circulatory migration, memory T cells can be divided into circulating cells and resident cells: circulating cells include central memory T cells (Tcm) and effector memory T cells (Tem), which can pass through blood and lymph in various tissues and organs of the body Circulate continuously; correspondingly, tissue-resident memory T cells (Trm) reside in non-lymphoid tissues under normal physiological conditions and do not exchange with circulating cells in the blood
.
Due to its special location advantages, Trm can play the first-line rapid barrier protection function against the infection of bacteria or tumors in the tissues where it resides (Masopust and Soerens, 2019)
.
Therefore, the research on regulating the differentiation and maintenance of Trm fate has considerable significance
.
T cell co-stimulatory molecule (Co-stimulatory molecule) signals can affect the differentiation and fate selection of initial T cells together with T cell receptors (TCR) and cytokines in the environment
.
Although there are many substantive research advances on cytokines and transcription factors that promote Trm production, whether there are specific costimulatory molecules and whether the interaction between cells in non-lymphoid tissues can induce the differentiation of the tissue-resident population Still unknown
.
In response to this issue, on December 20, 2021, the University of Minnesota Stephen Jameson's laboratory (the first author is PhD student Peng Changwei) published a titled Engagement of ICOS in tissues promotes establishment of CD8+ tissue-resident memory in Immunity.
The research article of T cells revealed that in the mouse acute infection model, the inducible costimulatory molecule ICOS can specifically mediate the efficient maturation and differentiation of CD8+ tissue-resident memory T cells in non-lymphoid tissues
.
The inducible costimulatory molecule ICOS has a clear role in the differentiation of CD4+ helper T cells, and it is essential for the differentiation of follicular helper cells (Tfh) in the germinal center response
.
However, the role of ICOS in the differentiation of CD8+ cytotoxic T cells remains unclear
.
First, through different acute infection models of viruses or bacteria, the researchers found that the number of CD8+ T cells deficient in ICOS was no different in the peripheral circulating memory T cells compared with the wild type.
However, the number of CD8+ T cells in non-lymphoid tissues However, the memory-retaining cells showed a significant lack of specificity
.
This finding is mutually corroborated by the high expression of the ICOS gene as a CD8+ resident cell in the previous report
.
Through the study of different time points after infection, it is further found that the absence or blocking of ICOS does not affect the initial activation of CD8+ T cells or the expansion of effector cells, and it can migrate to non-lymphatic tissues as effectively as wild-type at the initial stage of infection.
However, defects appear in the process of further differentiation and maturation in the subsequent tissues
.
In contrast, blocking the ICOS signal of mature CD8+ resident memory cells will not affect their long-term maintenance
.
In order to further determine the time and mechanism of the effect of ICOS on CD8+ resident memory cells, the researchers used adoptive transfer to show whether CD8+ T cells were co-stimulated by ICOS during the activation and proliferation stage in the lymphatic tissues at the initial stage of infection.
The signal has no effect on the subsequent maturation and differentiation into Trm in normal non-lymphoid tissues; on the contrary, adoptive transfer of CD8+ effector T cells that normally receive ICOS costimulatory signals into ICOS-L-deficient mice will have no effect on them.
The differentiation of Trm in lymphoid tissues is hindered
.
Since the ligand ICOS-L of ICOS is widely expressed in various antigen-presenting cells and stromal cells and epithelial cells of non-lymphoid tissues, it is difficult to determine the source of the ICOS costimulatory signal that mediates CD8+ Trm
.
Researchers through bone marrow chimera studies have shown that: unlike CD4+ Tfh, which uses B cells in lymphoid organs as the source of ICOS-L, the ICOS-L costimulatory signal of CD8+ Trm originates from non-lymphatic tissues that do not respond to radiation.
Sensitive cell populations-including cell populations derived from non-hematopoietic stem cells or antigen-presenting cells residing in tissues
.
Finally, through single-cell sequencing to compare wild-type and ICOS-deficient CD8+ T cells in the early stage of infection and mature memory stage, the researchers proved from the transcriptome that the CD8+ tissue-resident cells lacking ICOS are very different from wild-type CD8+ T cells.
Small
.
This reflects that ICOS, as a costimulatory signal in the tissue, mainly mediates the efficiency of the differentiation and maturation of CD8+ resident cells without affecting its quality
.
Further molecular mechanism studies have shown that the PI3K signal mediated by ICOS and its downstream transcription factor KLF2 play an important role in the tissue residence of CD8+ T cells
.
In summary, this study shows the role of the classical costimulatory molecule ICOS in the differentiation of CD8+ T lymphocytes-it can specifically and efficiently induce the production of resident memory cells in the tissue without affecting peripheral circulating memory cells
.
In addition, ICOS costimulatory signals mainly act after CD8+ T lymphocytes migrate to non-lymphoid tissues, and are mediated by local radiation-insensitive cell populations.
This is the role of the tissue microenvironment in the differentiation and maturation of tissue resident memory cells New avenues have been opened up
.
Due to the effectiveness of tissue-resident memory cells for vaccines and their high similarity with tumor infiltrating cells, the target of ICOS/ICOS-L costimulatory signals can become a new idea for the treatment of related diseases
.
Original link: https://doi.
org/10.
1016/j.
immuni.
2021.
11.
017 Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission.
The author has all legal rights , The offender must be investigated
.
