scholarly journals INDUCTION OF IMMUNOLOGICAL TOLERANCE TO A THYMUS-DEPENDENT ANTIGEN IN THE ABSENCE OF THYMUS-DERIVED CELLS

1974 ◽  
Vol 139 (5) ◽  
pp. 1303-1316 ◽  
Author(s):  
John W. Schrader
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Cell Function ◽  
Immunological Tolerance ◽  
Athymic Mice ◽  
Spleen Cells ◽  
Amplifying Effect ◽  
Bone Marrow Derived Cells

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5–10 mg of either FGG or DNP-HGG. Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive. Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG. The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.

scholarly journals GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

1974 ◽  
Vol 140 (3) ◽  
pp. 648-659 ◽  
Author(s):  
Judith A. Kapp ◽  
Carl W. Pierce ◽  
Stuart Schlossman ◽  
Baruj Benacerraf
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Cell Function ◽  
Suppressor Cells ◽  
Specific Response ◽  
Spleen Cells ◽  
X Irradiation

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice. Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.

scholarly journals Transcription factor Gfi-1 induced by G-CSF is a negative regulator of CXCR4 in myeloid cells

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2276-2285 ◽  
Author(s):  
Maria De La Luz Sierra ◽  
Paola Gasperini ◽  
Peter J. McCormick ◽  
Jinfang Zhu ◽  
Giovanna Tosato
Keyword(s):  
Bone Marrow ◽  
Dna Sequences ◽  
Peripheral Blood ◽  
Cell Function ◽  
Myeloid Cell ◽  
Cxcr4 Expression ◽  
Negative Regulator ◽  
Hematopoietic Stem

The mechanisms underlying granulocyte-colony stimulating factor (G-CSF)–induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood remain elusive. We provide evidence that the transcriptional repressor growth factor independence-1 (Gfi-1) is involved in G-CSF–induced mobilization of granulocytic lineage cells from the bone marrow to the peripheral blood. We show that in vitro and in vivo G-CSF promotes expression of Gfi-1 and down-regulates expression of CXCR4, a chemokine receptor essential for the retention of hematopoietic stem cells and granulocytic cells in the bone marrow. Gfi-1 binds to DNA sequences upstream of the CXCR4 gene and represses CXCR4 expression in myeloid lineage cells. As a consequence, myeloid cell responses to the CXCR4 unique ligand SDF-1 are reduced. Thus, Gfi-1 not only regulates hematopoietic stem cell function and myeloid cell development but also probably promotes the release of granulocytic lineage cells from the bone marrow to the peripheral blood by reducing CXCR4 expression and function.

scholarly journals MATURATION OF THE HUMORAL IMMUNE RESPONSE IN MICE

1974 ◽  
Vol 139 (2) ◽  
pp. 249-263 ◽  
Author(s):  
Patricia G. Spear ◽  
Gerald M. Edelman
Keyword(s):  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
Spleen Cells ◽  
Con A ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Humoral Antibodies

In spite of the prenatal appearance of immunoglobulin-bearing lymphocytes and θ-positive lymphocytes in the spleens of Swiss-L mice, these mice are not able to produce detectable levels of humoral antibodies in response to antigen until after 1 wk of age. Adult levels of response are not achieved until 4–8 wk of age. In the presence of bacterial lipopolysaccharides, which can substitute for or enhance T-cell function, the B cells from young Swiss-L mice were found to be indistinguishable in function from adult B cells, both with respect to the numbers of plaque-forming cells (PFC) produced in vitro in response to antigen and with respect to the kinetics of PFC induction. The spleen cells from young Swiss-L mice are significantly less sensitive than adult spleen cells, however, to stimulation by the T cell mitogens, concanavalin A (Con A) and phytohemagglutinin (PHA). Very few Con A-responsive cells could be detected at birth but the numbers increased sharply with age until 3 wk after birth. On the other hand, PHA-responsive cells could not be detected in the spleen until about 3 wk of age. The latter cells were found to respond also to Con A, but at a lower dose (1 µg/ml) than that required for the bulk of the Con A-responsive cells (3 µg/ml). The cells that respond both to PHA and to Con A appear in the spleen at about the time that Swiss-L mice acquire the ability to produce humoral antibodies, and these cells can be depleted from the spleen by the in vivo administration of antithymocyte serum. The development of humoral immune responses in these mice therefore appears to be correlated with the appearance of recirculating T lymphocytes that are responsive both to PHA and to Con A.

Suppression of NK Cell-Mediated Bone Marrow Cell Rejection by CD4+CD25+ Regulatory T Cells: Linkage of Adaptive to Innate Responses.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2195-2195
Author(s):  
William J. Murphy ◽  
Isabel Bareo ◽  
Alan M. Hanash ◽  
Lisbeth A. Welniak ◽  
Kai Sun ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Marrow Cell ◽  
Poly I:C ◽  
Hybrid Resistance

Abstract While a link between the innate to adaptive immune system has been established, studies demonstrating direct effects of T cells in regulating Natural Killer (NK) cell function have been lacking. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) have been shown to potently inhibit adaptive responses by T cells. We therefore investigated whether Tregs could affect NK cell function in vivo. Using a bone marrow transplantation (BMT) model of hybrid resistance, in which parental (H2d) marrow grafts are rejected by the NK cells of the F1 recipients (H2bxd), we demonstrate that the in vivo removal of host Tregs significantly enhances NK-cell mediated BM rejection. This heightened rejection was mediated by the specific NK cell Ly-49+ subset previously demonstrated to reject the BMC in this donor/host pairing. The depletion of Tregs could also further increase rejection already enhanced by treating recipients with the NK cell activator, poly I:C. Although splenic NK cell numbers were not significantly altered, increased splenic NK in vitro cytotoxic activity was observed from the recovered cells. The regulatory role of Tregs was confirmed in adoptive transfer studies in which transferred CD4+CD25+ Tregs resulted in abrogation of NK cell-mediated hybrid resistance. Thus, Tregs can potently inhibit NK cell function in vivo and their depletion may have therapeutic ramifications with NK cell function in BMT and cancer therapy.

scholarly journals INDUCTION OF A HEMOLYSIN RESPONSE IN VITRO

1970 ◽  
Vol 132 (6) ◽  
pp. 1267-1278 ◽  
Author(s):  
Klaus-Ulrich Hartmann
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
Cell Suspension ◽  
Cell Population ◽  
Cell Suspensions ◽  
Spleen Cells ◽  
Bone Marrow Derived Cells ◽  
Thymus Cells

The immune response to foreign erythrocytes was studied in vitro. Two subpopulations of cells were prepared. One was a population of bone marrow-derived spleen cells, taken from thymectomized, irradiated, and bone marrow-reconstituted mice; there was evidence that most of the precursors of the PFC had been present in this cell population, but few PFC developed in cultures of these cells alone in the presence of immunogenic erythrocytes. Another cell suspension was made from spleens of mice which had been irradiated and injected with thymus cells and erythrocytes; these cells were called educated T cells. The two cell suspensions together allow the formation of PFC in the presence of the erythrocytes which were used to educate the T cells, but not in the presence of noncross-reacting erythrocytes. If bone marrow-derived cells and T cells were kept in culture together with two different species of erythrocytes, and if one of the erythrocytes had been used to educate the T cells, then PFC against each of the erythrocytes could be detected.

scholarly journals Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

2008 ◽  
Vol 205 (13) ◽  
pp. 3187-3199 ◽  
Author(s):  
Lee-Hwa Tai ◽  
Marie-Line Goulet ◽  
Simon Belanger ◽  
Noriko Toyama-Sorimachi ◽  
Nassima Fodil-Cornu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Viral Infections ◽  
Plasmacytoid Dendritic Cell ◽  
Class I ◽  
Type I ◽  
Class I Mhc ◽  
Mhc Molecules

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo.

scholarly journals HIF-1α is a negative regulator of plasmacytoid DC development in vitro and in vivo

Blood ◽  
2012 ◽  
Vol 120 (15) ◽  
pp. 3001-3006 ◽  
Author(s):  
Andreas Weigert ◽  
Benjamin Weichand ◽  
Divya Sekar ◽  
Weixiao Sha ◽  
Christina Hahn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Function ◽  
Bone Marrow Cells ◽  
Negative Regulator ◽  
Low Oxygen ◽  
Hematopoietic Stem ◽  
Lineage Differentiation ◽  
Marrow Cells

Abstract Hypoxia-inducible factors (HIFs) regulate hematopoiesis in the embryo and maintain hematopoietic stem cell function in the adult. How hypoxia and HIFs contribute to hematopoietic lineage differentiation in the adult is ill defined. Here we provide evidence that HIF-1 limits differentiation of precursors into plasmacytoid dendritic cells (pDCs). Low oxygen up-regulated inhibitor of DNA binding 2 (ID2) and suppressed Flt3-L–induced differentiation of bone marrow cells to pDCs in wild-type but not HIF-1αfl/fl LysM-Cre bone marrow cells. Moreover, pDC differentiated normally in hypoxic ID2−/− bone marrow cultures. Finally, we observed elevated pDC frequencies in bone marrow, blood, and spleen of HIF-1αfl/fl LysM-Cre and ID2−/−, but not HIF-2αfl/fl LysM-Cre mice. Our data indicate that the low oxygen content in the bone marrow might limit pDC development. This might be an environmental mechanism to restrict the numbers of these potentially autoreactive cells.

scholarly journals Influence of Epinastine Hydrochloride, an -Receptor Antagonist, on the Function of Mite Allergen-Pulsed Murine Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Ken-Zaburo Oshima ◽  
Kazuhito Asano ◽  
Ken-Ichi Kanai ◽  
Miyuki Suzuki ◽  
Harumi Suzaki
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Clinical Status ◽  
Mouse Bone Marrow ◽  
Dc Functions ◽  
Receptor Antagonists ◽  
Murine Bone Marrow

There is established concept that dendritic cells (DCs) play essential roles in the development of allergic immune responses. However, the influence of receptor antagonists on DC functions is not well defined. The aim of the present study was to examine the effect of epinastine hydrochloride (EP), the most notable histamine receptor antagonists in Japan, onDermatophagoides farinae (Der f)-pulsed mouse bone marrow-derived DCs in vitro and in vivo. EP at more than 25 ng/mL could significantly inhibit the production of IL-6, TNF- and IL-10 fromDer f-pulsed DCs, which was increased byDer fchallenge in vitro. On the other hand, EP increased the ability ofDer f-pulsed DCs to produce IL-12. Intranasal instillation ofDer f-pulsed DCs resulted in nasal eosinophilia associated with a significant increase in IL-5 levels in nasal lavage fluids.Der f-pulsed and EP-treated DCs significantly inhibited nasal eosinophila and reduced IL-5. These results indicate that EP inhibits the development of Th2 immune responses through the modulation of DC functions and results in favorable modification of clinical status of allergic diseases.

Parasitology and immunology of mice vaccinated with irradiated Litomosoides sigmodontis larvae

Parasitology ◽  
2000 ◽  
Vol 120 (3) ◽  
pp. 271-280 ◽  
Author(s):  
L. LE GOFF ◽  
C. MARTIN ◽  
I. P. OSWALD ◽  
P. N. VUONG ◽  
G. PETIT ◽  
...  
Keyword(s):  
Immune Responses ◽  
Recovery Rate ◽  
Spleen Cells ◽  
Challenge Inoculation ◽  
Infective Larvae ◽  
Litomosoides Sigmodontis ◽  
Before And After ◽  
Type Response

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. II. A genetically restricted suppressor of mixed lymphocyte reactions released by alloantigen-activated spleen cells.

1975 ◽  
Vol 142 (6) ◽  
pp. 1391-1402 ◽  
Author(s):  
S S Rich ◽  
R R Rich
Keyword(s):  
Immune Responses ◽  
Mixed Lymphocyte Reaction ◽  
Antigenic Specificity ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Homology Relationship ◽  
Cell Suppression ◽  
Mixed Lymphocyte Reactions

The mechanism of alloantigen-activated spleen cell suppression of mixed lymphocyte reaction (MLR) is explored in this report. Activated murine suppressor spleen cells elaborated a soluble noncytotoxic factor which suppressed MLR responses by 55-95%. Generation of suppressor factor required both in vivo alloantigen sensitization and specific in vitro restimulation. Suppressor factor was not produced by activated spleen cells which had been treated with anti-Thy-1.2 serum and complement. Antigenic specificity toward alloantigens of the stimulator cells was not demonstrable. In contrast, suppressor factor effectively inhibited MLR response only of responder cells of those strains that shared the D-end and the I-C subregion of the H-2 complex with the cells producing suppressor factor. Therefore, active suppression appears to require an MHC-directed homology relationship between regulating and responder cells in MLR.

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