Abstract:
:FOXP3+ regulatory T cells (Tregs) constitute a critical barrier that enforces tolerance to both the self-peptidome and the extended-self peptidome to ensure tissue-specific resistance to autoimmune, allergic, and other inflammatory disorders. Here, we review intuitive models regarding how T cell antigen receptor (TCR) specificity and antigen recognition efficiency shape the Treg and conventional T cell (Tcon) repertoires to adaptively regulate T cell maintenance, tissue-residency, phenotypic stability, and immune function in peripheral tissues. Three zones of TCR recognition efficiency are considered, including Tcon recognition of specific low-efficiency self MHC-ligands, Treg recognition of intermediate-efficiency agonistic self MHC-ligands, and Tcon recognition of cross-reactive high-efficiency agonistic foreign MHC-ligands. These respective zones of TCR recognition efficiency are key to understanding how tissue-resident immune networks integrate the antigenic complexity of local environments to provide adaptive decisions setting the balance of suppressive and immunogenic responses. Importantly, deficiencies in the Treg repertoire appear to be an important cause of chronic inflammatory disease. Deficiencies may include global deficiencies in Treg numbers or function, subtle 'holes in the Treg repertoire' in tissue-resident Treg populations, or simply Treg insufficiencies that are unable to counter an overwhelming molecular mimicry stimulus. Tolerogenic vaccination and Treg-based immunotherapy are two therapeutic modalities meant to restore dominance of Treg networks to reverse chronic inflammatory disease. Studies of these therapeutic modalities in a preclinical setting have provided insight into the Treg niche, including the concept that intermediate-efficiency TCR signaling, high IFN-β concentrations, and low IL-2 concentrations favor Treg responses and active dominant mechanisms of immune tolerance. Overall, the purpose here is to assimilate new and established concepts regarding how cognate TCR specificity of the Treg repertoire and the contingent cytokine networks provide a foundation for understanding Treg suppressive strategy.
journal_name
Cell Immunoljournal_title
Cellular immunologyauthors
Mannie MD,DeOca KB,Bastian AG,Moorman CDdoi
10.1016/j.cellimm.2020.104173subject
Has Abstractpub_date
2020-09-01 00:00:00pages
104173eissn
0008-8749issn
1090-2163pii
S0008-8749(20)30333-6journal_volume
355pub_type
杂志文章,评审abstract::Several studies have demonstrated that addition of soluble anti-CD6 mAbs to 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated naive T cells can induce cell proliferation. We showed in the present study that cell proliferation in TPA-treated T cell cultures can be enhanced several fold when the anti-CD6 mAbs are eithe...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1995.0006
更新日期:1995-11-01 00:00:00
abstract::We have previously described a novel human B cell differentiation factor (BCDF), 446-BCDF, that is distinct biochemically and functionally from other cytokines. Since signal transduction pathways involved in human B cell differentiation have been incompletely studied and are poorly understood, we assessed the effects ...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1995.1050
更新日期:1995-04-15 00:00:00
abstract::Simultaneous stimulation of human monocytes/macrophages or THP1 cells with LPS and an antibody specific for the activation marker CD69 induces apoptosis. Here we demonstrate the involvement of multiple independent signals that are necessary for apoptosis induction. Thus, inhibitors of phospholipase A2 and lipoxygenase...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1996.0232
更新日期:1996-09-15 00:00:00
abstract::Endogenous retroviral superantigens such as vSAG-7 are highly stimulatory for T cells through interaction with the T cell receptor on the basis of V beta usage. Priming of adult MMTV 7-negative mice with vSAG-7-expressing cells has been shown to result in peripheral V beta 6/CD4+ T cell activation followed by toleranc...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1995.1164
更新日期:1995-09-01 00:00:00
abstract::Tumor necrosis factor (TNF) is a 17-kDa protein produced by endotoxin-stimulated macrophages. We have demonstrated that recombinant human TNF activates human macrophages to kill intracellular bacteria of the Mycobacterium avium complex (MAC) in a dose-related manner. TNF also primed macrophages to produce superoxide a...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(92)90243-i
更新日期:1992-10-15 00:00:00
abstract::The biochemical events leading to enhanced membrane expression of HLA-DR and CR3 by human peripheral blood monocytes (MO) following exposure to bacterial lipopolysaccharide (LPS) were examined. In a previous study we demonstrated that an increase in intracellular calcium was necessary, but not sufficient, for MO to in...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(87)90209-7
更新日期:1987-08-01 00:00:00
abstract::The severity of influenza increases with age, with worse disease in aged males than females. Testosterone concentrations decline with age in males, which may impact influenza pathogenesis. Aged male mice were treated with testosterone or placebo and outcomes during influenza A virus (IAV) infection were compared with ...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/j.cellimm.2019.103988
更新日期:2019-11-01 00:00:00
abstract::In view of the critical role played by bacillus Calmette-Guérin (BCG) in the development and functional activation of protective T cells against tuberculosis, it has become important to understand the mechanisms by which cytokines regulate BCG-mediated immune responses. There is evidence that cytokine-mediated suppres...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.2000.1662
更新日期:2000-06-15 00:00:00
abstract::A new mechanism for regulation of delayed-type hypersensitivity (DTH) was investigated. The subcutaneous injection without adjuvant of syngeneic epidermal Langerhans' cells (LC) pulsed with keyhole limpet hemocyanin (KLH) into BALB/c mice gave rise to DTH upon challenge of the ear with the same antigen. When such cell...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1993.1279
更新日期:1993-11-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/j.cellimm.2011.03.023
更新日期:2011-01-01 00:00:00
abstract::Abnormalities in immune response play a major role in the increased susceptibility to infection after hemorrhage and trauma. Infections occurring after injury often originate in the intestine. In order to determine the effects of hemorrhage on intestinal B cell function, we examined hemorrhage-induced alterations in a...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(90)90015-j
更新日期:1990-06-01 00:00:00
abstract::A series of Lyt 2+, trinitrophenyl (TNP)-specific T-cell lines are shown to lyse 51Cr-labeled target cells in an antigen-specific, H-2-restricted fashion in a 4-hr assay. These cells also produce lymphotoxin, in addition to other factors, upon stimulation with TNP-haptenated syngeneic splenocytes. A technique for intr...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(85)90389-2
更新日期:1985-06-01 00:00:00
abstract::Many studies have shown that tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation. Neuropeptide substance P (SP) has been known to exert significant influence on production of certain inflammatory cytokine by immune cells. Immunopathogenic mechanism underlying the effect of neu...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1995.9969
更新日期:1995-12-01 00:00:00
abstract::It has long been believed that mast cells play a crucial role in the development of many physiological changes during immediate allergic responses. This study was conducted to evaluate the anti-inflammation mechanism of Schizonepeta tenuifolia (ST) extract and ST purified chemicals on the PMA plus A23187-induced stimu...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/j.cellimm.2012.05.012
更新日期:2012-05-01 00:00:00
abstract::The pre-B cell stage of B lymphocyte development is characterized by the presence of immunoglobulin heavy chains of the IgM isotype in the cytoplasm and no other heavy or light chains in the cytoplasm or on the surface. We established several cell lines that were identical in their serologically defined pre-B cell phe...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(89)90253-0
更新日期:1989-04-01 00:00:00
abstract::We have investigated the ability of long-term cultured T helper (Th) cell lines to help an in vivo cytotoxic T lymphocyte (CTL) response to non-H-2 alloantigens (minor antigens). Th cell lines specific for various single or undefined minor antigens were selected by regular restimulation with antigen in vitro. They wer...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(84)90309-5
更新日期:1984-02-01 00:00:00
abstract::As fascinating a molecule as it can potentially get, nuclear factor-κB (NF-κB), a regulatory transcription factor, is as intriguing. NF-κB is a dimeric complex that controls the transcription of essential genes. NF-κB is involved in a variety of responses that play a pivotal role in regulating the immune response to i...
journal_title:Cellular immunology
pub_type: 杂志文章,评审
doi:10.1016/j.cellimm.2011.06.021
更新日期:2011-01-01 00:00:00
abstract::Upregulation of immunoglobulin D-specific receptors (IgD-R) on CD4+ T cells may facilitate their interaction with specific carbohydrate moieties uniquely associated with membrane IgD on B cells. Previous studies have shown that upregulation of IgD-R facilitates cognate T-B cell interactions by mediating bidirectional ...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.2000.1747
更新日期:2001-02-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(90)90198-z
更新日期:1990-08-01 00:00:00
abstract::We previously demonstrated that injection of a high dose (4 X 10(9] of sheep erythrocytes (SRBC) into C57BL/6 mice results in the generation of splenic B cells (plastic nonadherent, Thy-1- and Ig+) which, when transferred to normal syngeneic recipients, subsequently induce antigen-specific suppressor T cells to suppre...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(84)90242-9
更新日期:1984-01-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(84)90033-9
更新日期:1984-09-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(85)90164-9
更新日期:1985-01-01 00:00:00
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journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/j.cellimm.2013.01.004
更新日期:2013-01-01 00:00:00
abstract::Stimulation via the CD3/TCR molecular complex induces proliferation of resting T cells, but triggers programmed cell death (apoptosis) in immature thymocytes and preactivated mature T cells. Activation-induced cell death (AICD) triggered by anti-CD3/TCR mAb or by staphylococcus enterotoxin superantigen is associated w...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1995.9979
更新日期:1995-12-01 00:00:00
abstract::To improve the engraftment of human peripheral blood lymphocytes (PBL) to severe combined immunodeficient (SCID) mice, and to elucidate the factors which prevent the PBL's survival, we treated SCID mice with mAb, which neutralizes murine IFN-gamma's ability to activate cell-mediated immunity. Compared with untreated m...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1997.1238
更新日期:1998-01-10 00:00:00
abstract::Intravenous injection of spleen cells (SC) coated with an antitrinitrophenyl (anti-TNP) IgM monoclonal antibody, Sp6 (Sp6-SC), which carries a recurrent idiotype, resulted in activation of a Lyt-2-positive population which did adhere to Sp6-coated plates. No effect of Sp6-SC injection could be observed in vivo on an a...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(86)90314-x
更新日期:1986-04-01 00:00:00
abstract::The mechanism underlying the apparent differences in the capacity of murine and human class I MHC molecules to function as signal transducing structures in T cells was examined. Cross-linking murine class I MHC molecules on splenic T cells did not stimulate an increase in intracellular calcium ([Ca2+]i) and failed to ...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/0008-8749(92)90254-m
更新日期:1992-10-15 00:00:00
abstract::Previous investigations have demonstrated a strain-associated differential susceptibility to herpes simplex virus-1 (HSV-1) infection in mice; C57BL/6 mice are more resistant to infection than BALB/c mice. Despite considerable research dealing with the immune response to HSV-1, relatively little attention has been pai...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1994.1246
更新日期:1994-09-01 00:00:00
abstract::Neuroinflammation plays a pivotal role in the incidence and progression of Alzheimer's disease (AD). Cathelicidin-related antimicrobial peptide (CRAMP) is critically involved in the innate neuronal responses of chronic neuroinflammation in AD and thus plays a key role in the disease. Here, we show that Aβ42 induced mi...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1016/j.cellimm.2018.05.008
更新日期:2018-09-01 00:00:00
abstract::Antigen processing in B cells is initiated by antigen binding to the surface B cell antigen receptor (BCR). The BCR is a signaling receptor which also functions to endocytose bound antigen for subsequent intracellular processing and presentation with class II molecules. Previously, using subcellular fractionation, we ...
journal_title:Cellular immunology
pub_type: 杂志文章
doi:10.1006/cimm.1998.1264
更新日期:1998-02-25 00:00:00