Sympathetic neural signaling via the β2-adrenergic receptor suppresses T-cell receptor-mediated human and mouse CD8(+) T-cell effector function.

Abstract:

:Postganglionic sympathetic neurons innervate secondary lymphoid organs and secrete norepinephrine (NE) as the primary neurotransmitter. NE binds and signals through five distinct members of the adrenergic receptor family. In this study, we show elevated expression of the β2-adrenergic receptor (ADRB2) on primary human CD8(+) effector memory T cells. Treatment of both human and murine CD8(+) T cells with NE decreased IFN-γ and TNF-α secretion and suppressed their cytolytic capacity in response to T-cell receptor (TCR) activation. The effects of NE were specifically reversed by β2-specific antagonists. Adrb2(-/-) CD8(+) T cells were completely resistant to the effects of NE. Further, the ADRB2-specific pharmacological ligand, albuterol, significantly suppressed effector functions in both human and mouse CD8(+) T cells. While both TCR activation and stimulation with IL-12 + IL-18 were able to induce inflammatory cytokine secretion, NE failed to suppress IFN-γ secretion in response to IL-12 + IL18. Finally, the long-acting ADRB2-specific agonist, salmeterol, markedly reduced the cytokine secretion capacity of CD8(+) T cells in response to infection with vesicular stomatitis virus. This study reveals a novel intrinsic role for ADRB2 signaling in CD8(+) T-cell function and underscores the novel role this pathway plays in adaptive T-cell responses to infection.

journal_name

Eur J Immunol

authors

Estrada LD,Ağaç D,Farrar JD

doi

10.1002/eji.201646395

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

1948-58

issue

8

eissn

0014-2980

issn

1521-4141

journal_volume

46

pub_type

杂志文章
  • Hereditary complement C7 deficiency in nine families: subtotal C7 deficiency revisited.

    abstract::Deficiencies in terminal complement components, including the component C7, are uncommon and associated with an increased risk of recurrent systemic neisserial infection. A total of 22 molecular defects have been reported in the C7 gene with both complete (C7Q0) and subtotal (C7SD) C7 deficiencies. In this study we re...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636812

    authors: Rameix-Welti MA,Régnier CH,Bienaimé F,Blouin J,Schifferli J,Fridman WH,Sautès-Fridman C,Frémeaux-Bacchi V

    更新日期:2007-05-01 00:00:00

  • Monoclonal gammopathies in aging mu, kappa-transgenic mice: involvement of the B-1 cell lineage.

    abstract::Monoclonal gammopathies (MG) are monoclonal proliferative disorders of B cells at the differentiation stage of Ig production. They can be detected in the serum, either as transient or as persistent homogenous immunoglobulin (H-Ig) components. The exact phenotype, localization, and cell lineage origin of the precursor ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830270943

    authors: van Arkel C,Hopstaken CM,Zurcher C,Bos NA,Kroese FG,Savelkoul HF,Benner R,Radl J

    更新日期:1997-09-01 00:00:00

  • Bispecific F (ab')2 monomer prepared with anti-CD3 and anti-tumor monoclonal antibodies is most potent in induction of cytolysis of human T cells.

    abstract::Induction of cytolytic activity of peripheral blood mononuclear cells towards target cells was studied by preparing bispecific F(ab')2 which was composed of two Fab' fragments, one of which was derived from anti-CD3 monoclonal antibody and the other from anti-tumor monoclonal antibody. After reduction of the interchan...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830190814

    authors: Nitta T,Yagita H,Azuma T,Sato K,Okumura K

    更新日期:1989-08-01 00:00:00

  • Inhibition of proliferation and differentiation during early T cell development by anti-transferrin receptor antibody.

    abstract::Proliferating cells require iron and, therefore, express the transferrin receptor (CD71) that mediates cellular iron uptake. Cycling thymocytes, which have the CD4-8-3-, CD4-8+3-, or CD4+8+3- phenotypes, also express CD71. The importance of CD71-mediated iron uptake for proliferation and maturation of thymocytes was s...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830241147

    authors: Brekelmans P,van Soest P,Leenen PJ,van Ewijk W

    更新日期:1994-11-01 00:00:00

  • p49, a putative HLA class I-specific inhibitory NK receptor belonging to the immunoglobulin superfamily.

    abstract::NK cells display several killer inhibitory receptors (KIR) specific for different alleles of MHC class I molecules. A family of KIR are represented by type I transmembrane proteins belonging to the immunoglobulin superfamily (Ig-SF). Besides cDNA encoding for these KIR, additional cDNA have been identified which encod...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199806)28:06<1980::AID-IMM

    authors: Cantoni C,Verdiani S,Falco M,Pessino A,Cilli M,Conte R,Pende D,Ponte M,Mikaelsson MS,Moretta L,Biassoni R

    更新日期:1998-06-01 00:00:00

  • Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions.

    abstract::Endoglin is an homodimeric membrane antigen with capacity to bind transforming growth factor-beta (TGF-beta) and whose expression is up-regulated on myeloid cells upon differentiation to macrophages. We have isolated full-length cDNA clones from a lambda gt 10 library, prepared from phorbol 12-myristate 13-acetate-dif...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230943

    authors: Bellón T,Corbí A,Lastres P,Calés C,Cebrián M,Vera S,Cheifetz S,Massague J,Letarte M,Bernabéu C

    更新日期:1993-09-01 00:00:00

  • Differences and similarities in the A2.1-restricted cytotoxic T cell repertoire in humans and human leukocyte antigen-transgenic mice.

    abstract::HLA-A2.1-binding peptides (n = 38) were screened for immunogenicity with human peripheral blood mononuclear cells in cytotoxic T lymphocyte (CTL) induction experiments in vitro and with splenocytes from HLA-A2.1/Kb transgenic mice following immunization in vivo. These data were compiled and analyzed to determine the l...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260115

    authors: Wentworth PA,Vitiello A,Sidney J,Keogh E,Chesnut RW,Grey H,Sette A

    更新日期:1996-01-01 00:00:00

  • Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity.

    abstract::Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor immunotherapy. Here, we describe a novel genome-wide approach to identify multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors were examined for gene e...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200104)31:4<1239::aid-immu1239>3

    authors: Mathiassen S,Lauemøller SL,Ruhwald M,Claesson MH,Buus S

    更新日期:2001-04-01 00:00:00

  • Delay in expression of a mammary tumor provirus is responsible for defective clonal deletion during postnatal period.

    abstract::A gene-encoding ligand for deletion of T cells bearing TcRV beta 6 and V beta 8.1 cosegregates a new mammary tumor provirus locus, Mtv-50 in NC mice. The sequence of the open reading frame (ORF) in the 3' long terminal repeat (LTR) of Mtv-50 was strikingly similar to those of Mtv-7, Mtv-43 and exogenous mouse mammary ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830240235

    authors: Niimi N,Wajjwalku W,Ando Y,Tomida S,Takeuchi M,Ueda M,Kaneda T,Yoshikai Y

    更新日期:1994-02-01 00:00:00

  • Target structure for natural killer cells: evidence against a unique role for transferrin receptor.

    abstract::The transferrin receptor (TfR) was recently proposed as putative natural killer (NK) cell target structure. Here data are presented against this hypothesis and it is shown that low TfR expression and high NK sensitivity can occur concommitantly . K562 cells were studied at various stages of cell proliferation. No chan...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140412

    authors: Dokhélar MC,Garson D,Testa U,Tursz T

    更新日期:1984-04-01 00:00:00

  • Regulation of T helper-B lymphocyte adhesion through CD4-HLA class II interaction.

    abstract::Antigen-independent adhesion of CD4+ T lymphocytes to Epstein-Barr virus (EBV)-transformed B cells is mediated by CD2/lymphocyte function-associated antigen (LFA)-3 and LFA-1/intracellular adhesion molecule (ICAM)-1. Although some anti-CD4 antibodies block the antigen-independent adhesion of CD4+ T lymphocytes, the CD...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830200326

    authors: Mazerolles F,Amblard F,Lumbroso C,Lecomte O,Van de Moortele PF,Barbat C,Piatier-Tonneau D,Auffray C,Fischer A

    更新日期:1990-03-01 00:00:00

  • An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN-gamma.

    abstract::Tyrosine kinase 2 (Tyk2) contributes to the signals triggered by IL-12 for IFN-gamma production by NK cells and T cells. We found in this study that Tyk2-deficient (-/-) mice showed increased susceptibility at the early stage after an i.p. infection with Listeria monocytogenes, accompanied by impaired IFN-gamma produc...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636173

    authors: Aizu K,Li W,Yajima T,Arai T,Shimoda K,Nimura Y,Yoshikai Y

    更新日期:2006-11-01 00:00:00

  • Murine macrophage precursor characterization. I. Production, phenotype and differentiation of macrophage precursor hybrids.

    abstract::This study reports on the earliest stages of mononuclear phagocyte differentiation. A crucial question in this developmental process is whether mature macrophage (M phi) heterogeneity is already appointed at the precursor cell level. For this purpose, we produced clonal populations of mononuclear phagocytes from bone ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830200104

    authors: Leenen PJ,Slieker WA,Melis M,Van Ewijk W

    更新日期:1990-01-01 00:00:00

  • Recombinant interleukin (IL) 2-induced human B cell differentiation is mediated by autocrine IL6.

    abstract::The molecular mechanism of the interleukin (IL) 2-induced differentiation of human B cells has been investigated. The experimental results show that Staphylococcus aureus Cowan strain I (SAC) activation alone induces IL6 secretion from B cells. When B cells were activated by SAC, there was an increased transcription o...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830191215

    authors: Xia X,Lee HK,Clark SC,Choi YS

    更新日期:1989-12-01 00:00:00

  • Interleukin 2/interleukin 4-independent T helper cell generation during an in vitro antigenic stimulation of mouse spleen cells in the presence of cyclosporin A.

    abstract::Cyclosporin A (CsA), an immunosuppressive drug which completely suppresses the humoral response to thymus-dependent antigens, does not affect the generation of T helper (Th) cells during an in vitro stimulation of murine spleen cells with sheep red blood cells. The appearance of Th cells depends on time and their deve...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210304

    authors: Motta I,Colle JH,Shidani B,Truffa-Bachi P

    更新日期:1991-03-01 00:00:00

  • Relationship between the enhanced expression of histocompatibility antigens on interferon-treated L 1210 cells and their position in the cell cycle.

    abstract::We have determined the cell cycle position of individual mouse leukemia L 1210 cells by cytophotometric and autoradiographic techniques and simultaneously determined the amount of histocompatibility antigens expressed on the surface of individual cells by quantitative immunofluorescence. Interferon treatment of L 1210...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830060112

    authors: Killander D,Lindahl P,Lundin L,Leary P,Gresser I

    更新日期:1976-01-01 00:00:00

  • Specificity of an HLA-DRB1*0401-restricted T cell response to type II collagen.

    abstract::A panel of HLA-DRB1*0401-restricted CD4+ mouse T cell hybridomas specific for bovine type II collagen were generated from transgenic mice expressing the human HLA-DRA1*0101/-DRB1*0401 and CD4 molecules. The vast majority recognized a single peptide determinant corresponding to residues 261-273 (CII 261-273). This dete...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830260431

    authors: Fugger L,Rothbard JB,Sonderstrup-McDevitt G

    更新日期:1996-04-01 00:00:00

  • CD40 ligand is a T cell growth factor.

    abstract::CD40 ligand (CD40L) is a 33-kDa type II membrane glycoprotein induced on T cells upon activation. CD40L has previously been shown to induce proliferation of resting B cells, immunoglobulin (Ig) secretion from B cells cultured with cytokines and cytokine secretion and tumoricidal activity from monocytes. In this report...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230941

    authors: Armitage RJ,Tough TW,Macduff BM,Fanslow WC,Spriggs MK,Ramsdell F,Alderson MR

    更新日期:1993-09-01 00:00:00

  • Surface receptors identify mouse NK1.1+ T cell subsets distinguished by function and T cell receptor type.

    abstract::Natural killer T (NKT) lymphocytes rapidly produce several cytokines, including IL-4 and IFN-gamma, upon activation, and act as regulatory cells at an early interphase of innate and adaptive immune responses. They have been implicated as important elements in diverse immune responses including the regulation of autoim...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200323963

    authors: Stenström M,Sköld M,Ericsson A,Beaudoin L,Sidobre S,Kronenberg M,Lehuen A,Cardell S

    更新日期:2004-01-01 00:00:00

  • Physiology of murine B lymphocytes. I. Life-spans of anti-mu and haptenated Ficoll (thymus-independent antigen)-reactive B cells.

    abstract::We have evaluated the life-span of B lymphocytes by measuring the functional reactivity of normal B cells upon transfer into xid mice, which do not respond to anti-mu, fluoresceinated-Ficoll (FL-Ficoll) and 2,4,6-trinitrophenyl aminoethylcarbamylmethyl Ficoll (TNP-Ficoll). After 4 days of transfer only 30-40% of anti-...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830181019

    authors: Udhayakumar V,Goud SN,Subbarao B

    更新日期:1988-10-01 00:00:00

  • Homeostatic regulation of T effector to Treg ratios in an area of seasonal malaria transmission.

    abstract::An important aspect of clinical immunity to malaria is the ability to down-regulate inflammatory responses, once parasitaemia is under control, in order to avoid immune-mediated pathology. The role of classical (CD4(+)CD25(+)CD127(lo/-)FOXP3(+)) Treg in this process, however, remains controversial. Thus, we have chara...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200839112

    authors: Finney OC,Nwakanma D,Conway DJ,Walther M,Riley EM

    更新日期:2009-05-01 00:00:00

  • Optimizing anti-CD3 affinity for effective T cell targeting against tumor cells.

    abstract::Bispecific antibodies binding to the TCR/CD3 complex and to a tumor-associated surface molecule can be used to target cytotoxic T lymphocytes against tumor cells. We reasoned that high-affinity binding to CD3 may reduce the efficiency of T cell stimulation and target the bispecific reagent to T cells rather than to tu...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200211)32:11<3102::AID-IMMU3102>

    authors: Bortoletto N,Scotet E,Myamoto Y,D'Oro U,Lanzavecchia A

    更新日期:2002-11-01 00:00:00

  • Role of Ia. W39 in the interaction of antigen-presenting cells with T and B lymphocytes.

    abstract::Ia. W39 is a B cell differentiation antigen whose membrane expression is controlled by the xid gene. In this report we show that, analogous to its B cell expression, Ia. W39 is also present on a subset of Ia+ macrophages, indicating heterogeneity within that cell population. The Ir gene(s) for the antigenic determinan...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830120109

    authors: Huber BT,Rosenwasser LJ

    更新日期:1982-01-01 00:00:00

  • Reconstitution of genetically regulated responses against random and ordered synthetic polypeptides by methylated bovine serum albumin as analyzed by isoelectric focusing.

    abstract::In previous publications it was shown by avidity measurements, cross-reactivity patterns and genetic analyses, that the tetrapeptide T-T-G-G is the immuno-dominant epitope of the synthetic polypeptide (T, G)-A--L. In the present study this close immunological relationship between the random multichain copolymer (T, G)...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830060905

    authors: Cramer M,Schwartz M,Mozes E,Sela M

    更新日期:1976-09-01 00:00:00

  • Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T-rich phosphorothiate oligodeoxynucleotides.

    abstract::Toll-like receptors (TLR) 7 and 8 are closely related members of the TLR family of pathogen-associated molecular pattern recognition receptors and have an important function in activation of innate immune responses upon viral infection. TLR7 can be activated selectively by the guanosine analogue loxoribine, whereas th...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200535806

    authors: Jurk M,Kritzler A,Schulte B,Tluk S,Schetter C,Krieg AM,Vollmer J

    更新日期:2006-07-01 00:00:00

  • Role of inflammatory dendritic cells in innate and adaptive immunity.

    abstract::The major role of cells of the dendritic family in immunity and tolerance has been amply documented. Since their discovery in 1973, these cells have gained increasing interest from immunologists, as they are able to detect infectious agents, migrate to secondary lymphoid tissue, and prime naive T lymphocytes, thereby ...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.201242480

    authors: Hespel C,Moser M

    更新日期:2012-10-01 00:00:00

  • High connectivity, natural antibodies preferentially use 7183 and QUPC 52 VH families.

    abstract::Twenty-seven B cell hybridomas derived from spleen cells of nonimmunized, 6-day-old BALB/c mice and previously characterized serologically were screened for VH-gene expression: hybridomas expressing the two most D-proximal VH-gene families, 7183 and QUPC 52 were over-represented in this sample. Strikingly, clones sero...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830170315

    authors: Holmberg D

    更新日期:1987-03-01 00:00:00

  • Distinction between IL-13+ and IFN-gamma+ natural killer cells and regulation of their pool size by IL-4.

    abstract::The hypothesis that distinct subsets of NK cells produce type 2 and type 1 cytokines in resting naive lymphocytes was tested analyzing cytokine production at the single-cell level. Two non-overlapping IL-13+ and IFN-gamma+ subsets were identified in adult and neonatal NK cells. IL-2 maintained their relative proportio...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200202)32:2<413::AID-IMMU413>3.0

    authors: Loza MJ,Peters SP,Zangrilli JG,Perussia B

    更新日期:2002-02-01 00:00:00

  • Harnessing proteases for T regulatory cell immunotherapy.

    abstract::The immune system is tightly regulated by a subset of T cells defined as regulatory T cells (Tregs). Tregs maintain immune homeostasis by restraining unwarranted immune cell activation and effector function. Here, we discuss an important but underappreciated role of proteases in controlling Treg function. Proteases re...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审

    doi:10.1002/eji.201948270

    authors: Amarnath S,Brown ML

    更新日期:2020-06-01 00:00:00

  • A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice.

    abstract::Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27, IL-35) mitigate autoimmune diseases. Each IL-12 family member is comprised of an α and a β chain, and chain-sharing is a key feature. Although four ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201546095

    authors: Wang X,Wei Y,Xiao H,Liu X,Zhang Y,Han G,Chen G,Hou C,Ma N,Shen B,Li Y,Egwuagu CE,Wang R

    更新日期:2016-06-01 00:00:00