TY  - JOUR
AB  - It is well established that CD4 and CD8 T cells are required for the initiation of autoimmune diabetes in NOD mice. However, different subsets of CD4 or CD8 cells may play different roles in the initiation of insulitis. In this study, we evaluated the role of the previously described CD8(+) CD122(+) in this process. We found that prediabetic NOD mice have an almost 50% reduction of CD8(+) CD122(+) T cells in their secondary lymphoid organs compared with BL/6 or Balb/c mouse strains. This reduction is explained by the lack of the regulatory CD8(+) CD122(+) PD-1(+) cell population in the NOD mice, as we found that all CD8(+) CD122(+) T cells from prediabetic NOD mice lack PD-1 expression and regulatory function. Depletion of CD8(+) CD122(+) PD-1(-) cells through injection of anti-CD122 mAb in prediabetic female NOD mice reduced the infiltration of mononuclear cells into the Langerhans islets and delayed the onset and decreased the incidence of overt diabetes. In addition, we found that transfer of highly purified and activated CD8(+) CD122(+) PD-1(-) cells, together with diabetogenic splenocytes from NOD donors to NOD SCID recipients, accelerates the diabetes development in these mice. Together, these results demonstrate that CD8(+) CD122(+) PD-1(-) T cells from NOD mice are effector cells that are involved in the pathogenesis of autoimmune diabetes.
AU  - Arndt, B.*
AU  - Witkowski, L.*
AU  - Ellwart, J.W.
AU  - Seissler, J.
C1  - 42752
C2  - 35330
CY  - Bethesda
SP  - 111-120
TI  - CD8+ CD122+ PD-1- effector cells promote the development of diabetes in NOD mice.
JO  - J. Leukoc. Biol.
VL  - 97
IS  - 1
PB  - Federation Amer Soc Exp Biol
PY  - 2015
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - no Abstract
AU  - Crowe, S.M.*
AU  - Ziegler-Heitbrock, L.
C1  - 4344
C2  - 28340
SP  - 541-543
TI  - Editorial: Monocyte subpopulations and lentiviral infection.
JO  - J. Leukoc. Biol.
VL  - 87
IS  - 4
PB  - Federation Amer Soc Exp Biol
PY  - 2010
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - STAT1 is a key effector of cytokines involved in the resistance to pathogens; its identified transcriptional targets mediate the innate immune response involved in the defense against viruses and bacteria. Little is known about the role of STAT1 in adaptive immunity, including its impact on BCR or surface Ig expression. Analysis of this point is difficult in humans, as STAT1 deficiency is extremely rare. SD patients die early in childhood from a severe immunodeficiency. Herein, a SD B cell line obtained from a SD patient was compared with a B cell line from a STAT1-proficient subject in search of differences in surface Ig expression. In this SD B cell line, a complete absence of surface IgG was noted. The mRNA encoding the surface form of IgG was detected only in STAT1-proficient B cells; the mRNAs encoding the secreted and the surface forms were detected in SD and STAT1-proficient B cells. Re-expression of STAT1 in SD B cells restored surface IgG expression and a functional BCR. Conversely, shRNA silencing of STAT1 in B cells reduced considerably the expression of the surface IgG. Although limited to one B cell line, these results suggest that STAT1 may play an essential role in surface IgG expression in human B cells. Possible mechanisms involve regulation of mRNA splicing, transcription, or both. These observations extend the role of STAT1 further in adaptive immunity, including the regulation of BCR expression.
AU  - Najjar, I.*
AU  - Deglesne, P.A.*
AU  - Schischmanoff, P.O.*
AU  - Fabre, E.E.*
AU  - Boisson-Dupuis, S.*
AU  - Nimmerjahn, F.*
AU  - Bornkamm, G.W.
AU  - Dusanter-Fourt, I.*
AU  - Fagard, R.*
C1  - 5382
C2  - 28400
SP  - 1145-1152
TI  - STAT1-dependent IgG cell-surface expression in a human B cell line derived from a STAT1-deficient patient.
JO  - J. Leukoc. Biol.
VL  - 87
IS  - 6
PB  - Federation Amer Soc Exp Biol
PY  - 2010
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - The MAPK phosphatase DUSP1 is an essential negative regulator of TLR-triggered innate immune activation. Here, we have investigated the impact of DUSP1 on inflammatory and antimicrobial host responses to the intracellular pathogen Chlamydophila pneumoniae. Following nasal infection, DUSP1-deficient mice mounted an enhanced pulmonary cytokine (IL-1beta, IL-6) and chemokine response (CCL3, CCL4, CXCL1, CXCL2), leading to increased leukocyte infiltration. Of interest, the increased inflammatory response, in the absence of DUSP1, was associated with higher bacterial numbers in the lungs, although the expression of IFN-gamma and critical antichlamydial effector molecules, such as iNOS, was intact. Blockade of IL-6 trans-signaling by injection of a soluble gp130-Fc fusion protein corrected the overshooting chemokine production as well as the increased chlamydial load in Dusp1(-/-) mice. Furthermore, IL-6 enhanced the replication of C. pneumoniae in embryonic fibroblasts in vitro. These data show that DUSP1 is required to achieve a balanced response to chlamydial infection and identify IL-6 as critical for amplifying inflammation and benefiting chlamydial growth through direct effects on infected cells.
AU  - Rodriguez, N.
AU  - Dietrich, H.
AU  - Mossbrugger, I.*
AU  - Weintz, G.
AU  - Scheller, J.*
AU  - Hammer, M.*
AU  - Quintanilla-Martinez, L.
AU  - Rose-John, S.*
AU  - Miethke, T.*
AU  - Lang, R.*
C1  - 5507
C2  - 27726
SP  - 579-587
TI  - Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1(-/-) mice: Critical role of IL-6.
JO  - J. Leukoc. Biol.
VL  - 88
IS  - 3
PB  - Federation Amer. Soc. Exp. Biol.
PY  - 2010
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - The adhesion receptor CD226 (DNAM-1) is a member of the Ig superfamily possessing two extracellular V-like domains. In humans, CD226 was shown to be expressed by NK as well as T cells. During T cell priming, CD226-mediated costimulatory signals may skew the subsequent differentiation into the Th1 pathway. In addition, CD226 expressed on NK and cytotoxic T cells is engaged by its counter-receptor CD155, present on target cells, thereby triggering their elimination. We established mAb specifically recognizing mCD226, demonstrating that CD226 is expressed by precursor and mature but not developing T cells. In contrast, NK cells are distinguished by a rather heterogeneous CD226 expression profile. In addition, expression of CD226 appears coupled to that of other NK cell receptors, as high expression of CD226 was found to correlate with decreased proportions of Ly49D and H positive NK cells. Upon injection into mice, the anti-CD226 antibodies caused selective depletion of CD8(+) T cells. Moreover, these antibodies as well as a naturally occurring CD226 splice variant lacking the outermost V-like domain were instrumental in determining that CD226 adheres to CD155 via its first domain. In addition, antibodies were identified as capable of blocking the CD226/CD155 interaction and to prevent NK-driven killing of immature DC. CD226 is thus the first mNK receptor identified to be essential for the elimination of this particular cell type.
AU  - Seth, S.*
AU  - Georgoudaki, A.M.*
AU  - Chambers, B.J.*
AU  - Qiu, Q.*
AU  - Kremmer, E.
AU  - Maier, M.K.*
AU  - Czeloth, N.*
AU  - Ravens, I.*
AU  - Foerster, R.*
AU  - Bernhardt, G.*
C1  - 682
C2  - 26521
SP  - 91-101
TI  - Heterogeneous expression of the adhesion receptor CD226 on murine NK and T cells and its function in NK-mediated killing of immature dendritic cells.
JO  - J. Leukoc. Biol.
VL  - 86
IS  - 1
PB  - Federation Amer Soc Exp Biol
PY  - 2009
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - Macrophages in the airways form an important element of immune defense and inflammation. We analyzed induced sputum from airways of patients with CF for the types of macrophages present, their receptor expression, and phagocytic function. In samples from patients and age-matched controls, macrophages were analyzed by multicolor flow cytometry, scavenger receptor expression was studied at the protein and mRNA level, and receptor function was investigated using fluorescent particles. In adult patients with CF, we discovered a pronounced expansion of the small CD14+ DR+ CD68weak+ macrophages to 73 +/- 18% compared with 16 +/- 8% in healthy controls. Expression of the MARCO and CD206 (mannose receptor) was strongly reduced at the mRNA and protein level in sputum macrophages. Antibody-blocking studies showed that MARCO mediates phagocytosis of unopsonized particles. In line with reduced MARCO expression, sputum macrophages in CF showed a deficient uptake of particles (23 +/- 9% of cells) compared with healthy controls (71 +/- 15%). The deficiency of MARCO expression in the predominant small sputum macrophages in CF may lead to impaired clearance of inhaled particles with increased inflammation and damage to the CF lung.
AU  - Wright, A.K.A.*
AU  - Rao, S.*
AU  - Range, S.*
AU  - Eder, C.M.S.
AU  - Hofer, T.P.
AU  - Frankenberger, M.
AU  - Kobzik, L.*
AU  - Brightling, C.*
AU  - Grigg, J.*
AU  - Ziegler-Heitbrock, L.
C1  - 600
C2  - 26452
CY  - BETHESDA
SP  - 479-489
TI  - Pivotal Advance: Expansion of small sputum macrophages in CF: Failure to express MARCO and mannose receptors.
JO  - J. Leukoc. Biol.
VL  - 86
IS  - 3
PB  - Federation Amer Soc Exp Biol
PY  - 2009
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - Alternate splicing of STAT1 produces two isoforms: alpha, known as the active form, and beta, previously shown to act as a dominant-negative factor. Most studies have dealt with STAT1alpha, showing its involvement in cell growth control and cell death. To examine the specific function of either isoform in cell death, a naturally STAT1-deficient human B cell line was transfected to express STAT1alpha or STAT1beta. STAT1alpha, expressed alone, enhanced cell death, potentiated the fludarabine-induced apoptosis, and enhanced the nuclear location, the phosphorylation, and the transcriptional activity of p53. Unexpectedly, STAT1beta, expressed alone, induced cell death through a mechanism that was independent of the nuclear function of p53. Indeed, in STAT1beta-expressing B cells, p53 was strictly cytoplasmic where it formed clusters, and there was no induction of the transcriptional activity of p53. These data reveal a novel role of STAT1beta in programmed cell death, which is independent of p53.
AU  - Najjar, I.*
AU  - Schischmanoff, P.O.*
AU  - Baran-Marszak, F.*
AU  - Deglesne, P.A.*
AU  - Youlyouz-Marfak, I.*
AU  - Pampin, M.*
AU  - Feuillard, J.*
AU  - Bornkamm, G.W.
AU  - Chelbi-Alix, M.K.*
AU  - Fagard, R.*
C1  - 3744
C2  - 28402
SP  - 1604-1612
TI  - Novel function of STAT1β in B cells: Induction of cell death by a mechanism different from that of STAT1α.
JO  - J. Leukoc. Biol.
VL  - 84
IS  - 6
PB  - Federation Amer Soc Exp Biol
PY  - 2008
SN  - 0741-5400
ER  - 

TY  - JOUR
AB  - Blood monocyte subpopulations have been defined in man initially, and the two major types of monocytes are the CD14++ CD16- and the CD14+ CD16+ monocytes. These cells have been shown to exhibit distinct phenotype and function, and the CD14+ CD16+ were labeled proinflammatory based on higher expression of proinflammatory cytokines and higher potency in antigen presentation. The current review describes these properties, including the relationship to dendritic cells, and summarizes the host of publications about CD14+ CD16+ monocytes in inflammation and infectious disease in man, all of which suggest a crucial role of these cells in the disease processes. The review also covers the more recent description of homologues of these cells in other model species, which is expected to better define the role of monocyte subsets in disease.
AU  - Ziegler-Heitbrock, L.
C1  - 2527
C2  - 24971
SP  - 584-592
TI  - The CD14+ CD16+ blood monocytes: Their role in infection and inflammation.
JO  - J. Leukoc. Biol.
VL  - 81
IS  - 3
PB  - FASEB
PY  - 2007
SN  - 0741-5400
ER  - 

TY  - JOUR
AU  - Dayyani, F.*
AU  - Joeinig, A.*
AU  - Ziegler-Heitbrock, L.
AU  - Schmidmaier, R.*
AU  - Straka, C.*
AU  - Emmerich, B.*
AU  - Meinhardt, G.*
C1  - 3657
C2  - 22274
SP  - 207-213
TI  - Autologous stem-cell transplantation restores the functional properties of CD14+CD16+ monocytes in patients with myeloma and lymphoma.
JO  - J. Leukoc. Biol.
VL  - 75
PY  - 2004
SN  - 0741-5400
ER  - 

TY  - JOUR
AU  - Hofer, T.P.
AU  - Bitterle, E.
AU  - Beck-Speier, I.
AU  - Maier, K.L.
AU  - Frankenberger, M.
AU  - Heyder, J.
AU  - Ziegler-Heitbrock, L.
C1  - 3193
C2  - 21841
SP  - 856-864
TI  - Diesel exhaust particles increase LPS-stimulated COX-2 expression and PGE2 production in human monocytes.
JO  - J. Leukoc. Biol.
VL  - 75
PY  - 2004
SN  - 0741-5400
ER  - 

TY  - JOUR
AU  - Dayyani, F.*
AU  - Belge, K.-U.*
AU  - Frankenberger, M.
AU  - Mack, M.*
AU  - Berki, T.*
AU  - Ziegler-Heitbrock, L.*
C1  - 10067
C2  - 21314
SP  - 33-39
TI  - Mechanism of glucocorticoid-induced depletion of human CD14+CD16+ monocytes.
JO  - J. Leukoc. Biol.
VL  - 74
PY  - 2003
SN  - 0741-5400
ER  - 

TY  - JOUR
AU  - Schabath, R.*
AU  - Müller, G.*
AU  - Schubel, A.*
AU  - Kremmer, E.
AU  - Lipp, M.*
AU  - Forster, R.*
C1  - 21600
C2  - 19731
SP  - 996-1004
TI  - The murine chemokine receptor CXCR4 is tightly regulated during T cell development and activation.
JO  - J. Leukoc. Biol.
VL  - 66
PY  - 1999
SN  - 0741-5400
ER  -