About this Research Topic
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.
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.
Keywords: Memory T cells, chronic infection, latent infection, tumor, T cell exhaustion
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.
