Human circulating and tissue-resident memory CD8+ T cells

Abstract

Our current knowledge of human memory CD8 + T cells is derived largely from studies of the intravascular space. However, emerging data are starting to challenge some of the dogmas based on this work, suggesting that a conceptual revision may be necessary. In this review, we provide a brief history of the field and summarize the biology of circulating and tissueresident memory CD8 + T cells, which are ultimately responsible for effective immune surveillance. We also incorporate recent findings into a biologically integrated model of human memory CD8 + T cell differentiation. Finally, we address how future innovative human studies could improve our understanding of anatomically localized CD8 + T cells to inform the development of more effective immunotherapies and vaccines, the need for which has been emphasized by the global struggle to contain SARS-CoV-2.

Hist2Cell: Deciphering Fine-grained Cellular Architectures from Histology Images

“…2.d). Note that these highly predictable cell types have critical functions in the human airway system, for example, CD8 EM cells are essential in directly eliminating infected or malignant cells in situ [27], and ciliated cells play a pivotal role in airway homeostasis by trapping and expelling microorganisms, mucus and other debris [28]. Systematically, we also found Hist2Cell excelled in predicting the abundance for cell types exhibiting a higher spatial auto-correlation denoted by Moran’s I (i.e., spatially variable cell types, as detailed in Fig.…”

The integrated stress response/eIF2a pathway controls cytokine production in tissue-resident memory CD4+T cells

“…Memory T cells were divided into two distinct populations, central memory T (Tcm) and effector memory (Tem) cells, which can be distinguished based on specific homing capacity and effector functions (1). In the last decade, tissue-resident memory T (Trm) cells were described as a distinct memory T cell subset (2)(3)(4)(5)(6).…”

“…In contrast to Tcm and Tem cells, which survey peripheral tissues by recirculating through the blood and lymph, Trm cells do not recirculate and exhibit long-term persistence at sites of previous infections. It is now well established that Trm cells provide long-term immunity against local reinfections (2)(3)(4)(5)(6), but they also contribute to organ-specific immunopathology in relapsing immune-mediated inflammatory diseases of the gut (7), central nervous system (8), skin (9,10), and kidney (11)(12)(13). The local production of cytokines by CD4 + Trm cells orchestrates protective tissue immunity against invading pathogens, but can also promote hyperinflammation and tissue damage in immune-mediated inflammatory diseases (14)(15)(16)(17)(18).…”

Immune perturbations in human pancreas lymphatic tissues prior to and after type 1 diabetes onset

“…Human immunophenotypes associated with T1D include T cell [11][12][13] , B cell 14,15 , and natural killer (NK) cell 16 perturbations as well as accelerated immunological aging 17 in peripheral blood mononuclear cells (PBMCs). While surveying PBMCs can be informative, the immune system operates primarily within tissue microenvironments and disease-specific signatures may not be fully recapitulated in circulating immune cells [18][19][20][21][22] . Indeed, pancreatic islets of T1D individuals contain β cell antigen-specific CD8+ T cells 23 , and the frequency of CD8+ T cells that recognize β cell antigens in the pancreas, not the blood, distinguishes T1D from healthy donors 24 .…”