Research Topic

Characterization, Functions, and Roles of Antigen-Specific Regulatory T Cells in Health and Disease

About this Research Topic

Regulatory T cells (Tregs) play an essential role in homeostasis, particularly in protecting the host from self-destructive, over-aggressive immune responses using both direct and indirect mechanisms. Initially, there was a widely held simplistic view of these cells. Tregs were thought to be are a homogeneous population of CD4+CD25+ T cells that developed in the thymus (tTregs), had self-antigen specificity, and migrated only to lymphoid tissues.

Growing evidence suggests that Tregs represent a heterogeneous population of T cells that can also develop in the periphery with non-self specificity, allowing them to control antigen-specific immune responses. Some studies have demonstrated that antigen-specific Tregs are 100 times more potent compared to self-specific Tregs. These cells also differ from naïve tTreg in that they migrate into tissues to suppress specific cells. The expansion and/or creation antigen-specific Tregs, through genetic (e.g. expression of chimeric antigen receptors or T cell receptors) and non-genetic manipulation, has been the focus of several groups who wish to direct the specificity and function of Tregs to specific cells/tissues to avoid global immunosuppression.

This year marks the 30th anniversary of the discovery that CD4+CD25+ Tregs contribute to organ transplant tolerance. Since then, preclinical studies have highlighted the efficacy of Tregs in autoimmune settings and in preventing graft rejection. This research has now been extended to several clinical trials assessing the efficacy of polyclonally expanded and donor alloreactive specific Tregs. These clinical trials have demonstrated the safety and efficacy of ex vivo expanded polyclonal Treg administration in type-1 diabetic, liver, kidney, and bone marrow transplant recipients.

Despite the positive outcomes ex vivo, more research is required to determine the efficacy of antigen-specific Tregs in vivo. Furthermore, several key questions around antigen-specific Treg subsets remain unanswered, including an understanding of their homing capacity, their in vivo targets as well as their suppressive mechanism pathways and stability. An understanding of the aforementioned will help inform their optimal therapeutic use.

In this Research Topic, we welcome the submission of Original Research, Review, Mini Review, and Perspective articles that address, but are not limited to, the following topics:

1. Defining antigen-specificity in Tregs efficacy in vivo and in vitro
2. Molecular and cellular pathways involved in the activation of antigen-specific Tregs
3. Suppressive mechanisms utilized by antigen-specific Tregs
4. Defining in vivo cellular targets of antigen-specific Tregs
5. Novel methods for isolating and expanding antigen-specific Tregs
6. Genetic engineering of antigen-specific Treg subsets to create novel immunotherapies
7. Imaging modalities to address the in vivo location and migration of antigen-specific Tregs
8. Strategies to enhance the potency of antigen-specific Treg, e.g. cytokine or microbial components


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Regulatory T cells (Tregs) play an essential role in homeostasis, particularly in protecting the host from self-destructive, over-aggressive immune responses using both direct and indirect mechanisms. Initially, there was a widely held simplistic view of these cells. Tregs were thought to be are a homogeneous population of CD4+CD25+ T cells that developed in the thymus (tTregs), had self-antigen specificity, and migrated only to lymphoid tissues.

Growing evidence suggests that Tregs represent a heterogeneous population of T cells that can also develop in the periphery with non-self specificity, allowing them to control antigen-specific immune responses. Some studies have demonstrated that antigen-specific Tregs are 100 times more potent compared to self-specific Tregs. These cells also differ from naïve tTreg in that they migrate into tissues to suppress specific cells. The expansion and/or creation antigen-specific Tregs, through genetic (e.g. expression of chimeric antigen receptors or T cell receptors) and non-genetic manipulation, has been the focus of several groups who wish to direct the specificity and function of Tregs to specific cells/tissues to avoid global immunosuppression.

This year marks the 30th anniversary of the discovery that CD4+CD25+ Tregs contribute to organ transplant tolerance. Since then, preclinical studies have highlighted the efficacy of Tregs in autoimmune settings and in preventing graft rejection. This research has now been extended to several clinical trials assessing the efficacy of polyclonally expanded and donor alloreactive specific Tregs. These clinical trials have demonstrated the safety and efficacy of ex vivo expanded polyclonal Treg administration in type-1 diabetic, liver, kidney, and bone marrow transplant recipients.

Despite the positive outcomes ex vivo, more research is required to determine the efficacy of antigen-specific Tregs in vivo. Furthermore, several key questions around antigen-specific Treg subsets remain unanswered, including an understanding of their homing capacity, their in vivo targets as well as their suppressive mechanism pathways and stability. An understanding of the aforementioned will help inform their optimal therapeutic use.

In this Research Topic, we welcome the submission of Original Research, Review, Mini Review, and Perspective articles that address, but are not limited to, the following topics:

1. Defining antigen-specificity in Tregs efficacy in vivo and in vitro
2. Molecular and cellular pathways involved in the activation of antigen-specific Tregs
3. Suppressive mechanisms utilized by antigen-specific Tregs
4. Defining in vivo cellular targets of antigen-specific Tregs
5. Novel methods for isolating and expanding antigen-specific Tregs
6. Genetic engineering of antigen-specific Treg subsets to create novel immunotherapies
7. Imaging modalities to address the in vivo location and migration of antigen-specific Tregs
8. Strategies to enhance the potency of antigen-specific Treg, e.g. cytokine or microbial components


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

30 October 2020 Abstract
26 March 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 October 2020 Abstract
26 March 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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