Immunological memory by CD8 T cells is a unique and fundamental prerequisite of the adaptive immune system. The underlying principle is that exposure to a pathogen leads to the generation of long-lived memory T cells, which provide an immediate and stronger immune response following re-encounter of the same pathogen ensuring effective protection following a pathogen infection or vaccination. The improved immunity arises as a result of increased precursor frequencies and functionality of antigen-specific memory T cells, such as increased cytokine production and cytotoxicity. However, the superior T cell response is also due to the diversification of the antigen-specific T cell pool into distinct types of memory T cells with differential ability to home to both secondary lymphoid organs and non-lymphoid frontline tissues. Indeed, long-lived antigen-specific T cells are retained in secondary lymphoid organs as stem-cell or central memory T cells, in vascular circulation as effector-memory T cells, or embedded in various non-lymphoid tissues as tissue-resident memory T cells. This classification corresponds with distinct phenotypic and functional characteristics including longevity, the capacity to self-renew, the expression of memory-associated surface molecules, and the ability to activate effector function. Importantly, a common feature of all subsets of memory T cells is thought to be their ability to be sustained in a quiescent yet ‘ready-to-respond’ state in the absence of antigen. Thus, classic memory T cells arise exclusively following resolution of an infection.
In contrast, chronic viral infections and tumor growth are characterized by the persistence of antigen inducing a long-term effector response that can lead to the induction of T cell exhaustion – a functional adaption of T cells characterized by impaired effector function and expression of inhibitory receptors, most notably PD-1. Importantly, chronic stimulation of T cells was thought to preclude the formation of memory T cells. Yet, recent work has identified T cells within long-term effector populations that contain features of memory. As such, these cells, distinguishable by the expression of the transcription factor T-cell factor 1 (TCF1) or the chemokine receptor CXCR5, retain proliferative potential and the ability to self-renew. Thus, these cells continuously replenish the pool of antigen-specific T cells with effector cells that can mediate viral control. Interestingly, these TCF1+ T cells can also exhibit features of T cell exhaustion as described for many actively persisting viral infections such as Human Immunodeficiency Virus (HIV) and Hepatitis B or C in humans, Lymphocytic choriomeningitis virus (LCMV) infections in mice, and tumors both in humans and mice. Most importantly, TCF1+ T cells are responsible for the boost of immunity following checkpoint blockade in immunotherapy.
In this Research Topic we welcome Review, Mini-Review, and Original Research articles that cover, but are not limited to, the following topics:
- Generation, differentiation and maintenance of memory T cells in models of antigen persistence such as active and latent chronic infections, tumors;
- Functional and transcriptional characterization of (exhausted) or long-lived memory T cells;
- Immunotherapeutic targeting of T cells in chronic infections and tumors;
- Therapeutic interventions boosting memory T cell formation for adoptive CAR T cell therapy.
Immunological memory by CD8 T cells is a unique and fundamental prerequisite of the adaptive immune system. The underlying principle is that exposure to a pathogen leads to the generation of long-lived memory T cells, which provide an immediate and stronger immune response following re-encounter of the same pathogen ensuring effective protection following a pathogen infection or vaccination. The improved immunity arises as a result of increased precursor frequencies and functionality of antigen-specific memory T cells, such as increased cytokine production and cytotoxicity. However, the superior T cell response is also due to the diversification of the antigen-specific T cell pool into distinct types of memory T cells with differential ability to home to both secondary lymphoid organs and non-lymphoid frontline tissues. Indeed, long-lived antigen-specific T cells are retained in secondary lymphoid organs as stem-cell or central memory T cells, in vascular circulation as effector-memory T cells, or embedded in various non-lymphoid tissues as tissue-resident memory T cells. This classification corresponds with distinct phenotypic and functional characteristics including longevity, the capacity to self-renew, the expression of memory-associated surface molecules, and the ability to activate effector function. Importantly, a common feature of all subsets of memory T cells is thought to be their ability to be sustained in a quiescent yet ‘ready-to-respond’ state in the absence of antigen. Thus, classic memory T cells arise exclusively following resolution of an infection.
In contrast, chronic viral infections and tumor growth are characterized by the persistence of antigen inducing a long-term effector response that can lead to the induction of T cell exhaustion – a functional adaption of T cells characterized by impaired effector function and expression of inhibitory receptors, most notably PD-1. Importantly, chronic stimulation of T cells was thought to preclude the formation of memory T cells. Yet, recent work has identified T cells within long-term effector populations that contain features of memory. As such, these cells, distinguishable by the expression of the transcription factor T-cell factor 1 (TCF1) or the chemokine receptor CXCR5, retain proliferative potential and the ability to self-renew. Thus, these cells continuously replenish the pool of antigen-specific T cells with effector cells that can mediate viral control. Interestingly, these TCF1+ T cells can also exhibit features of T cell exhaustion as described for many actively persisting viral infections such as Human Immunodeficiency Virus (HIV) and Hepatitis B or C in humans, Lymphocytic choriomeningitis virus (LCMV) infections in mice, and tumors both in humans and mice. Most importantly, TCF1+ T cells are responsible for the boost of immunity following checkpoint blockade in immunotherapy.
In this Research Topic we welcome Review, Mini-Review, and Original Research articles that cover, but are not limited to, the following topics:
- Generation, differentiation and maintenance of memory T cells in models of antigen persistence such as active and latent chronic infections, tumors;
- Functional and transcriptional characterization of (exhausted) or long-lived memory T cells;
- Immunotherapeutic targeting of T cells in chronic infections and tumors;
- Therapeutic interventions boosting memory T cell formation for adoptive CAR T cell therapy.
