Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function

Rahimi, Rod A.; Luster, Andrew D.

doi:10.1016/bs.ai.2018.02.002

Cited by 33 publications

(18 citation statements)

References 79 publications

(129 reference statements)

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“…Taken together, several models have been proposed for the generation of memory T lymphocytes. It is conceivable that more than one of these models contribute to memory T cell development in vivo, and may be influenced by factors such as TCR signal strength and inflammatory conditions in the microenvironment (cytokines), and in addition, costimulatory signals (e.g., CD28 family) [77] and other environmental cues, such as chemokines and even the microbiota from the tissue in which a T cell is activated [78][79][80].…”

Section: T-bet the Master-regulator Of Th1 Cells Acts In An Expressmentioning

confidence: 99%

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Raphael

Joern

Forsthuber

2020

Cells

121

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CD4 + T helper (Th) cells play central roles in immunity in health and disease. While much is known about the effector function of Th cells in combating pathogens and promoting autoimmune diseases, the roles and biology of memory CD4 + Th cells are complex and less well understood. In human autoimmune diseases such as multiple sclerosis (MS), there is a critical need to better understand the function and biology of memory T cells. In this review article we summarize current concepts in the field of CD4 + T cell memory, including natural history, developmental pathways, subsets, and functions. Furthermore, we discuss advancements in the field of the newly-described CD4 + tissue-resident memory T cells and of CD4 + memory T cells in autoimmune diseases, two major areas of important unresolved questions in need of answering to advance new vaccine design and development of novel treatments for CD4 + T cell-mediated autoimmune diseases.

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Section: T-bet the Master-regulator Of Th1 Cells Acts In An Expressmentioning

confidence: 99%

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Raphael

Joern

Forsthuber

2020

Cells

121

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“…In addition, and similar to Rubcn -/- macrophages, Rubcn -/- DCs significantly upregulated pro-inflammatory cytokines and chemokines, compared to Rubcn +/+ DCs (Martinez et al, 2011a; Martinez et al, 2016b). Specifically, Rubcn -/- DCs upregulated factors known to promote CD8 + T cell recruitment (such as Ccl2 , Ccl3 , Ccl4 , Cxcl9 , and Cxcl10 ) and activation (such as Il1b , Il6 , Il12b , and Tnf ) (Figure 1C, S1E) (Rahimi and Luster, 2018; Turner et al, 2014). Consistent with previous reports (Hayashi et al, 2018), Rubcn -/- DCs produced less IFNβ than Rubcn +/+ DCs (Figure 1C, S1E).…”

Section: Resultsmentioning

confidence: 99%

Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

Zhao

et al. 2019

Preprint

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41Major Histocompatibility Complex I (MHC-I) molecules classically present peptides derived from 42 endogenous antigens, but exogenous antigens can also gain access to the MHC-I machinery in 43 dendritic cells (DCs), which can activate antigen-specific CD8 + T cells. This process, termed 44 cross-presentation, can be triggered by the uptake of dying autologous cells, including tumor cells, 45by DCs. The molecular mechanisms that underlie efficient cross-presentation remain largely 46 uncharacterized, and an improved understanding of these mechanisms might reveal novel 47 strategies for anti-tumor therapies. Rubicon (RUBCN) is a molecule required for LC3-associated 48 phagocytosis (LAP), but dispensable for canonical autophagy, and mice lacking this protein 49 develop an autoimmune inflammatory pathology with age. Here, we demonstrate that Rubcn-50 deficient DCs have increased retention of engulfed cellular cargo in immature phagosomes 51 resulting in increased phagosome-to-cytosol escape and antigen access to proteasome-mediated 52 degradation. As a result, mice selectively lacking Rubcn in DCs mount stronger tumor antigen-53 specific CD8 + T cell responses and exhibit decreased tumor burden compared to wild type 54 littermates. These findings identify LAP as a key regulator of cross-presentation and suggest that 55 targeting RUBCN might represent a novel strategy for anti-tumor therapy.The ability of the immune system to distinguish between self and non-self is integral to maintaining 75 homeostasis and eradicating exogenous threats. Antigen-presenting cells (APCs), specifically 76 DCs, educate the host's adaptive immune response in a controlled and antigen-specific manner. 77CD8 + T cells are activated by peptides generated from intracellular antigens and presented in the 78 context of MHC-I. Peptides derived from healthy self-antigens presented to CD8 + T cells in the 79 periphery elicit a minimal or absent response, as CD8 + T cells expressing T cell receptors (TCRs) 80 that recognize self-antigens undergo negative selection in the thymus prior to their population of 81 the periphery (Rock et al., 2016). However, when cells are infected by virus or are transformed 82 by an oncogene, they can produce proteins that are not considered self, such as virus-encoded 83 proteins, and the presentation of these aberrant antigens via MHC-I activates a robust CD8 + T 84 cell response (Hansen and Bouvier, 2009). Therefore, the MHC-I pathway represents an 85 evolutionarily conserved mechanism that serves as a quality control mechanism for endogenous 86 proteins and viral defense (Kaufman, 2018). 88As the activation of CD8 + T cells is largely limited to their localization within secondary lymphoid 89 tissues, they must rely on the migration of patrolling APCs to deliver antigens to them (Hansen 90 and Bouvier, 2009). Classically, exogenous antigens are sensed as foreign, phagocytosed, 91 processed by the endosomal-lysosomal network, and loaded onto MHC-II molecules to stimulate 92 antigen-specific activation of CD4 + T cel...

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“…Chemokines and chemokine receptors are implicated in the mobilization and localization of immune cells to peripheral tissues and the generation of memory response. [21][22][23] While a role for CXCR6 in CD8 + T cell resident memory responses has been reported in infectious disease models, [24][25][26] there are no studies that directly address if specific chemokine receptors facilitate resident memory response by driving localization or retention of CD8 + T cells in cancerous tissues. Our current study addresses this gap and identified CXCR6 as the predominant chemokine receptor expressed by CD8 + Trm cells in human ovarian cancer, and their presence in tumors is associated with increased survival.…”

Section: Introductionmentioning

confidence: 99%

CXCR6 by increasing retention of memory CD8⁺ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer

Muthuswamy

McGray

Battaglia

et al. 2021

J Immunother Cancer

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PurposeResident memory CD8 T cells, owing to their ability to reside and persist in peripheral tissues, impart adaptive sentinel activity and amplify local immune response, and have beneficial implications for tumor surveillance and control. The current study aimed to clarify the less known chemotactic mechanisms that govern the localization, retention, and residency of memory CD8 T cells in the ovarian tumor microenvironment.Experimental designRNA and protein expressions of chemokine receptors in CD8+ resident memory T cells in human ovarian tumor-infiltrating CD8+ T cells and their association with survival were analyzed. The role of CXCR6 on antitumor T cells was investigated using prophylactic vaccine models in murine ovarian cancer.ResultsChemokine receptor profiling of CD8+CD103+ resident memory tumor-infiltrating lymphocytes in patients with ovarian cancer revealed high expression of CXCR6. Analysis of The Cancer Genome Atlas (TCGA) (ovarian cancer database revealed CXCR6 to be associated with CD103 and increased patient survival. Functional studies in mouse models of ovarian cancer revealed that CXCR6 is a marker of resident, but not circulatory, tumor-specific memory CD8+ T cells. CXCR6-deficient tumor-specific CD8+ T cells showed reduced retention in tumor tissues, leading to diminished resident memory responses and poor control of ovarian cancer.ConclusionsCXCR6, by promoting retention in tumor tissues, serves a critical role in resident memory T cell-mediated immunosurveillance and control of ovarian cancer. Future studies warrant exploiting CXCR6 to promote resident memory responses in cancers.

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Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function

Cited by 33 publications

References 79 publications

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

CXCR6 by increasing retention of memory CD8⁺ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer

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Chemokines: Critical Regulators of Memory T Cell Development, Maintenance, and Function

Cited by 33 publications

References 79 publications

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Memory CD4+ T Cells in Immunity and Autoimmune Diseases

Non-canonical autophagy in dendritic cells restricts cross-presentation and anti-tumor immunity

CXCR6 by increasing retention of memory CD8+ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer

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CXCR6 by increasing retention of memory CD8⁺ T cells in the ovarian tumor microenvironment promotes immunosurveillance and control of ovarian cancer