Hallmarks of Tissue-Resident Lymphocytes

Abstract

Although they are classically viewed as continuously recirculating through the lymphoid organs and blood, lymphocytes also establish residency in non-lymphoid tissues, most prominently at barrier sites, including the mucosal surfaces and skin. These specialized tissue-resident lymphocyte subsets span the innate-adaptive continuum and include innate lymphoid cells (ILCs), unconventional T cells (e.g., NKT, MAIT, γδ T cells, and CD8αα+IELs), and tissue-resident memory T (TRM) cells. Although these diverse cell types differ in the particulars of their biology, they nonetheless exhibit important shared features, including a role in the preservation of tissue integrity and function during homeostasis, infection, and non-infectious perturbations. In this Review, we discuss the hallmarks of tissue-resident innate, innate-like, and adaptive lymphocytes, as well as their potential functions in non-lymphoid organs.

Immunological memories of the bone marrow

“…It is interesting to note that in the recent hype about “tissue‐resident” memory T lymphocytes, bone marrow‐resident memory T lymphocytes were largely disregarded, quasi the “Cinderella” of memory lymphocytes 154, 155, 156, 157, 158, 159…”

Developing Connections among B Lymphocytes and Deregulated Pathways in Autoimmunity

“…In human atheroma, a local B cell differentiation process was found to take place in arterial walls, and adventitial oligoclonal resident B cells of atherosclerotic patients were mainly mature B-2 cells that lacked markers of terminal differentiation to plasma cells (17). Even in patients with aortic stenosis, which shares several B-1a cells (11 These characteristics are reminiscent of "tissue-resident cells" that represent the innate and adaptive branches of immunity and differ in their distribution in nonlymphoid tissues, yet exhibit common "innate"-like properties (13). For example, a combination of approaches has revealed that tissue-resident, "unconventional" or "innate-like" T cells express T cell receptors of limited diversity and recognize antigens in the context of nonclassical, nonpolymorphic MHC-like molecules (14).…”

Lifelong protection mediated by stem cell-like CD8+ T memory subset cells (Tscm) induced by vaccination

“…These studies demonstrate that T RM cells are located in the peripheral non-lymphoid tissues most often occupied by microbes at the outset of an infection, and respond immediately to the infection. The existence of different subsets of T memory cells present in the various tissue compartments as blasts or effector T cells, with distinct properties, tissueresidency "zip codes" and motilities, optimizes pathogen detection (2,3). Their existence can be seen as helpful for the development of new therapeutic interventions and vaccination technologies.…”

“…Like naive T cells, they patrol secondary lymphoid organs and undergo a rapid proliferative burst when their T cell antigen receptors recognize antigen-presenting molecules and then differentiate into effector cells (3). At this stage, they lose their lymph node homing receptors (CD62L and CCR7) and migrate to peripheral non-lymphoid tissues where they can destroy invading pathogens or transformed cells by means of effector cytokines or cytolysis of infected host cells (2,3). T cell recirculation is a dynamic process that is regulated during all phases of the immune response and is crucial in the fight against pathogens or transformed cells (4).…”

“…One could view immune cells as sentinels distributed over the entire body. The saying "tell me where you live and I'll tell you who you are" could well apply to the distinctive functions of different components of the immune system because cells of the immune system not only circulate continuously through the tissues but also establish tissue-resident populations of memory T (T RM ) cells that mount a first response against an intruder (2).…”