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Review
. 2019 Apr 26:37:521-546.
doi: 10.1146/annurev-immunol-042617-053214. Epub 2019 Feb 6.

Tissue-Resident T Cells and Other Resident Leukocytes

David Masopust  1 , Andrew G Soerens  1
Affiliations
Review

Tissue-Resident T Cells and Other Resident Leukocytes

David Masopust et al. Annu Rev Immunol. .

Abstract

Resident memory T (Trm) cells stably occupy tissues and cannot be sampled in superficial venous blood. Trm cells are heterogeneous but collectively constitute the most abundant memory T cell subset. Trm cells form an integral part of the immune sensing network, monitor for local perturbations in homeostasis throughout the body, participate in protection from infection and cancer, and likely promote autoimmunity, allergy, and inflammatory diseases and impede successful transplantation. Thus Trm cells are major candidates for therapeutic manipulation. Here we review CD8+ and CD4+ Trm ontogeny, maintenance, function, and distribution within lymphoid and nonlymphoid tissues and strategies for their study. We briefly discuss other resident leukocyte populations, including innate lymphoid cells, macrophages, natural killer and natural killer T cells, nonclassical T cells, and memory B cells. Lastly, we highlight major gaps in knowledge and propose ways in which a deeper understanding could result in new methods to prevent or treat diverse human diseases.

Keywords: T lymphocytes; immunity; lymphoid cells; memory; residence.

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Figures

Figure 1
Figure 1
Memory T cell migration properties. Memory T cells can be classified into subsets based on their migration patterns. Central memory T (Tcm) cells recirculate through blood and constitutively migrate through lymph nodes (LNs) using high endothelial venules. Effector memory T (Tem) cells are also found in blood and exhibit diverse migration properties, but they do not enter uninflamed lymph nodes via high endothelial venules. Resident memory T (Trm) cells do not recirculate and remain local occupants of tissues during the steady state. See Table 1 for distinct and overlapping characteristics of Tcm, Tem, and Trm cells.
Figure 2
Figure 2
Tools for studying resident memory T (Trm) cells. Trm cells are defined by migration properties, not cell surface markers, which makes them difficult to identify. Four common techniques, along with their strengths and weaknesses for interpretation, are summarized here: (a) parabiosis surgery, (b) transplantation, (c) intravascular staining, and (d) in situ labeling.
Figure 2
Figure 2
Tools for studying resident memory T (Trm) cells. Trm cells are defined by migration properties, not cell surface markers, which makes them difficult to identify. Four common techniques, along with their strengths and weaknesses for interpretation, are summarized here: (a) parabiosis surgery, (b) transplantation, (c) intravascular staining, and (d) in situ labeling.
Figure 3
Figure 3
Trm cells form part of an integrated tissue surveillance network that participates in tissue monitoring and disease. (a) Trm cells signal disruptions in tissue homeostasis and communicate with the diverse motley crew of host resident and circulating parenchymal, stromal, and leukocyte populations. (b) Trm cells are thus putative contributors to (and perhaps instigate or sustain) responses in tissues, where they may play favorable or unfavorable roles in diverse human disease conditions. Abbreviations: DC, dendritic cell; GVHD, graft-versus-host disease; ILC, innate lymphoid cell; NK, natural killer; Trm, resident memory T.
Figure 4
Figure 4
Trm ontogeny and function. (a) Naive T cells are primed to proliferate in secondary lymphoid organs. Some, but likely not all, daughter cells that migrate to nonlymphoid tissues possess the developmental potential to differentiate into Trm cells. This occurs under the influence of developmental cues encountered after migration. Some cues may be tissue specific, imparting regional differences between Trm cells occupying different locations. (b) When established Trm cells recognize cognate antigen, they communicate this information to neighboring cells and also mount regionalized anamnestic responses. Outcomes include cytokine production; killing antigen-bearing host cells; activation of endothelium to recruit leukocytes; activation of local DCs, NK cells, and bystander T cells; and egress of DCs to draining lymph nodes. Trm cells also undergo in situ proliferation that can result in the amplification of local memory (independent of Tcm cells) and progeny that egress out of nonlymphoid tissue. Some of those progeny remain Trm cells within the draining lymph node. Abbreviations: DC, dendritic cell; NK, natural killer; Tcm, central memory T; Tem, effector memory T; Trm, resident memory T.
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