scholarly journals Accessory and stimulating properties of dendritic cells and macrophages isolated from various rat tissues

1982 ◽  
Vol 156 (1) ◽  
pp. 1-19 ◽  
Author(s):  
WEF Klinkert ◽  
JH LaBadie ◽  
WE Bowers
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cell Activity ◽  
Accessory Cell ◽  
Nonspecific Esterase ◽  
Rat Tissues ◽  
Low Density ◽  
Γ Irradiation ◽  
Accessory Cells ◽  
Ia Antigens

Single cell suspensions of rat lymphoid and nonlymphoid tissues were fractionated on discontinuous gradients of bovine serum albumin into high density and low density subfractions. In general, accessory activity required for responses of periodate-treated T lymphocytes was recovered only in a low density population containing a small percent of the total fractionated cells from lymph nodes, spleen, liver, skin, and peritoneal exudates. Further purification always led to an increase of both accessory activity and number of dendritic cells present in nonrosetting and nonadherent populations. After purification, a high recovery of the total accessory activity was found in fractions that contained a high percentage of dendritic cells resulting in a more than 1,000-fold enrichment in accessory activity per cell. No other fraction obtained during the purification contained significant accessory activity. In all cases, macrophage-enriched populations lacked accessory cell activity. With the exception of peritoneal exudate cell preparations, which contained an inhibitory cell, the level of accessory activity in a given population was always found to be a function of the number of dendritic cells present. Dendritic cells from all sources were nonadherent, nonphagocytic, radio- resistant, and nonspecific esterase negative. They expressed Ia antigens and lacked Fc receptors. Both epidermal and lymph node dendritic cells contain Birbeck granules, subcellular structures previously described only for Langerhans cells. Accessory activity requires viable dendritic cells but is unaffected by 1,000 rad of γ-irradiation. However, ultraviolet irradiation abolished the activity of accessory cells. The cells that responded to periodate were IgG-negative T cells, whereas IgG-positive B cells could not be stimulated under the same conditions. Only periodate-treated T cells and dendritic cells were needed for responses to occur; removal of virtually all macrophages from these purified preparations had no effect. Dendritic cells were also required as stimulators in mixed leukocyte cultures, whereas macrophages, even though Ia positive, were inert.

scholarly journals A small number of anti-CD3 molecules on dendritic cells stimulate DNA synthesis in mouse T lymphocytes.

1989 ◽  
Vol 169 (3) ◽  
pp. 1153-1168 ◽  
Author(s):  
N Romani ◽  
K Inaba ◽  
E Puré ◽  
M Crowley ◽  
M Witmer-Pack ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Dna Synthesis ◽  
Specific Antigen ◽  
Accessory Cell ◽  
Binding Studies ◽  
Cell Clones ◽  
Accessory Cells ◽  
Cell Assays

Resting T cells enter cell cycle when challenged with anti-CD3 mAb and accessory cells that bear required Fc receptors (FcR). Presentation of anti-CD3 is thought to be a model for antigens presented by accessory cells to the TCR complex. We have obtained evidence that the number of anti-CD3 molecules that are associated with the accessory cell can be very small. We first noticed that thymic dendritic cells and cultured, but not freshly isolated, epidermal Langerhans cells (LC) were active accessory cells for responses to anti-CD3 mAb. DNA synthesis was abrogated by a mAb to the FcR but not by mAb to other molecules used in clonally specific antigen recognition, i.e., class I and II MHC products or CD4 and CD8. The requisite FcR could be identified on the LC but in small numbers. Freshly isolated LC had 20,000 FcR per cell, while the more active cultured LC had only 2,000 sites, using 125I-anti-FcR mAb in quantitative binding studies. Individual LC had similar levels of FcR, as evidenced with a sensitive FACS. FcR could not be detected on T cells or within the dendritic cell cytoplasm, at the start of or during the mitogenesis response. When the response was assessed at 30 h with single cell assays, at least 20 T cells became lymphoblasts per added LC, and at least 8 T cells were synthesizing DNA while in contact with the LC in discrete cell clusters. To the extent that anti-CD3 represents a polyclonal model for antigen presentation to specific T cell clones, these results suggest two conclusions. First, only 200-300 molecules of ligand on dendritic cells may be required to trigger a T cell. Second, the maturation of LC in culture entails "sensitizing" functions other than ligand presentation (anti-CD3 on FcR) to clonotypic T cell receptors.

scholarly journals Primary Dendritic Cells Phagocytose Cryptococcus neoformans via Mannose Receptors and Fcγ Receptor II for Presentation to T Lymphocytes

2002 ◽  
Vol 70 (11) ◽  
pp. 5972-5981 ◽  
Author(s):  
Rachel M. Syme ◽  
Jason C. L. Spurrell ◽  
Ernest K. Amankwah ◽  
Francis H. Y. Green ◽  
Christopher H. Mody
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cryptococcus Neoformans ◽  
Mannose Receptor ◽  
Dendritic Morphology ◽  
Accessory Cell ◽  
Adherent Cell ◽  
Fcγ Receptor ◽  
Pathogenic Yeast ◽  
Accessory Cells

ABSTRACT Different “professional” antigen-presenting cells (APC) have unique characteristics that favor or restrict presentation of microbial antigens to T cells, depending on the organism. Cryptococcus neoformans is a pathogenic yeast that presents unique challenges to APC, including its large size, its rigid cell wall, and its ability to stimulate T cells as a mitogen. T-cell proliferation in response to the C. neoformans mitogen (CnM) requires phagocytosis and processing of the organisms by accessory cells prior to presentation of CnM to T cells. Because of the requirement for uptake of the organism and more limited costimulatory requirements of mitogens, macrophages might be the most likely cellular source for the accessory cell. However, the present study demonstrates that a transiently adherent cell that was CD3−, CD14−, CD19−, CD56−, HLA-DR+, and CD83+ with a dendritic morphology, rather than monocyte-derived or tissue (alveolar) macrophages, was the most efficient APC for presentation of CnM. A large number of these cells bound and internalized the organism, and only a small number of dendritic cells were required for presentation of the mitogen to T cells. Further, the mannose receptor and Fcγ receptor II were required for presentation of C. neoformans, as blocking either of these receptors abrogated both uptake of C. neoformans and lymphocyte proliferation in response to CnM. These studies demonstrate the surprising fact that dendritic cells are the most efficient accessory cells for CnM.

scholarly journals Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants.

1980 ◽  
Vol 152 (6) ◽  
pp. 1779-1794 ◽  
Author(s):  
R J Hodes ◽  
K S Hathcock ◽  
A Singer
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibody Responses ◽  
Accessory Cell ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Histocompatibility Complex ◽  
Accessory Cells ◽  
Ia Antigens

The functional role of cell surface Ia antigens has been studied for in vitro antibody responses, using as a probe the ability of anti-Ia reagents to inhibit these responses. A hybridoma monoclonal anti-Ia reagent specific for a product of I-Ak (Ia.17) profoundly inhibited in vitro antibody responses to TNP-KLH by spleen cells of the I-Ak but not I-Ab haplotype. This inhibition by anti-I-Ak product, but not by interaction with T or B cell product, in spite of the fact that functional B cells as well as accessory cells could be shown to express the determinant detected by this hybridoma reagent. These results suggest that the Ia expressed by accessory cells in of unique functional importance in these responses. To further characterize the function of Ia antigens in this response system, the mechanism of anti-I-Ak inhibition was determined. The inhibition resulting from interaction of anti-I-Ak with accessory cell Ia was not mediated by nonspecific suppressor cells, nor was there nonspecific interference with accessory cell function as a result of the binding of anti-Ia antibody. The relationship between anti-Ia inhibition and T helper cell recognition of self determinations on accessory cells was analyzed using T cells from radiation bone marrow chimeras. It was demonstrated that (B10 X B10.A)F1 leads to B10 (F1 leads to B10) chimera T cells were able to cooperate with B10 (H-2b and I-Ab) but not B10.A (H-2a and I-Ak) accessory cells for responses to TNP-KLH; F1 leads to B10.A T cells were able to cooperate with B10.A but not B10 accessory cells; and both chimera populations were able to cooperate with (B10 X B10.A)F1 (F1) accessory cells. Monoclonal anti-I-Ak inhibited the cooperation of F1 leads to B10.A T cells with the same F1 accessory cells. Thus, inhibition by anti-I-Ak is dependent upon active helper T cell recognition of I-Ak-encoded determinants expressed on accessory cells. These findings demonstrate that T cells recognize self Ia determinants expressed on accessory cells, and that such recognition is required for the generation of T cell-dependent antibody responses.

scholarly journals Allogeneic mixed lymphocyte reactions during a second round of ontogeny: normal accessory cells did not restore defective interleukin- 2 (IL-2) synthesis in T cells but induced responsiveness to exogeneous IL-2

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2278-2284 ◽  
Author(s):  
S Cayeux ◽  
S Meuer ◽  
A Pezzutto ◽  
M Korbling ◽  
R Haas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Autologous Bone Marrow Transplantation ◽  
Interleukin 2 ◽  
Autologous Bone Marrow ◽  
Intrinsic Defect ◽  
Accessory Cell ◽  
Accessory Cells ◽  
Autologous Bone ◽  
Mixed Lymphocyte Reactions

Abstract The T-cell-accessory-cell interaction in mixed lymphocyte cultures was investigated in 25 patients following autologous bone marrow transplantation (ABMT) using autologous bone marrow treated in vitro with the cyclophosphamide derivative ASTA Z 7557. In a previous study using the same group of patients, T cells failed to synthesize interleukin-2 (IL-2) and proliferate in response to CD3- and CD2- mediated stimuli even in the presence of exogenous IL-2. To investigate whether this defect in IL-2 synthesis and proliferation was caused by defective cell-to-cell interactions, we analyzed mixed lymphocyte reactions (MLR) using T cells and irradiated non-T cells. When normal T cells from 10 different healthy subjects were challenged with allogeneic normal non-T cells, IL-2 production and proliferation were observed. In contrast, when normal T cells were cultured with non-T cells derived from patients found between 20 and 330 days after ABMT, no IL-2 secretion and no proliferative responses could be seen. The addition of lymphokines such as interleukin-1 (IL-1), interleukin-3 (IL- 3), tumor necrosis factor (TNF), granulocyte-macrophage colony stimulating factor (GM-CSF), and interferon-gamma (IFN-y) did not improve the reactions. Furthermore, when patients' T cells were incubated with normal, irradiated non-T cells, defective IL-2 synthesis or proliferative response was obtained. However, when IL-2 was added to these cultures, an improvement in proliferative reactions was observed. Taken together, these new data provide additional evidence that T cells early in ontogeny possessed an intrinsic defect in IL-2 synthesis and that physical cell-to-cell contact between patients' T cells and allogeneic accessory cells induced functional responsiveness to exogeneous IL-2.

Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1342-1349 ◽  
Author(s):  
Frank Osterroth ◽  
Annette Garbe ◽  
Paul Fisch ◽  
Hendrik Veelken
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Light Chain ◽  
Cytotoxic T Cells ◽  
Killer Cell ◽  
Cell Activity ◽  
Expression Vectors ◽  
Target Cells ◽  
Fab Fragment ◽  
Specific Lysis

Because of their hypervariable regions and somatic mutations, the antigen receptor molecules of lymphomas (idiotypes) are tumor-specific antigens and attractive targets for antilymphoma immunotherapy. For the optimal induction of human idiotype-specific cytotoxic T cells (CTL), idiotype was presented to CD8+ peripheral blood mononuclear cells by monocyte-derived autologous dendritic cells (DC) after the endocytosis of idiotype protein or by idiotype-expressing DC. Recombinant idiotype was obtained as a functionally folded Fab fragment by periplasmic expression in Escherichia coli. Idiotype-expressing DC were generated by transduction with recombinant Semliki forest virus vectors encompassing heavy- or light-chain idiotype genes. Autologous lymphoblastoid cell lines stably transfected with Epstein-Barr virus-based idiotype expression vectors were used as target cells to detect idiotype-specific lysis. CTL stimulated with idiotype-loaded DC showed strong specific, CD8-mediated, and major histocompatibility complex (MHC) class I-restricted cytotoxicity against autologous heavy- and light-chain idiotype. In contrast, stimulation with idiotype-transduced DC resulted in only moderate natural killer cell activity. These data confirm the existence of idiotype-specific CTL in patients with lymphoma, define a “good manufacturing practice”-compatible protocol for the generation of these cells without the requirement of viable lymphoma cells, and favor the processing of exogenous antigen over DC transduction for the induction of MHC I-restricted CTL against idiotypes with unknown antigenicity.

Tumor-induced alteration in macrophage accessory cell activity on autoreactive T cells

1989 ◽  
Vol 30 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Andrew D. Yurochko ◽  
Prakash S. Nagarkatti ◽  
Mitzi Nagarkatti ◽  
Klaus D. Elgert
Keyword(s):  
T Cells ◽  
Cell Activity ◽  
Accessory Cell ◽  
Autoreactive T Cells

G-CSF Activated Granulocytes Inhibit Experimental Graft-versus-Host Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4989-4989
Author(s):  
Zilton F.M. Vasconcelos ◽  
Julia Farache ◽  
Bruna M. Santos Grad ◽  
Tereza S. Palmeira Grad ◽  
Luis Fernando Bouzas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Activity ◽  
Control Group ◽  
Low Density ◽  
Graft Versus Host ◽  
The One

Abstract Acute Graft versus host diseas (aGVHD) is a major complication of stem cell transplantation. The disease is mediated by T cells and a higher incidence/severity would be expected when higher numbers of T cells are inoculated. However, the incidence of aGVHD in PBST, which carries about 10 times more T cells then BMT, is not higher than the one found in later. This finding indicates a modulatory role for G-CSF over T cell activity. We had previously shown that T cells from G-CSF treated PBSC donors do not produce g-IFN nor IL-4 and that this inhibition was mediated by low density, G-CSF activated, granulocytes. In order to test if in fact G-CSF activated granulocytes could inhibit disease, we first checked if G-CSF could generate low density granulocytes, in vivo and in vitro. Indeed, either in vivo(21mg /day - 5 days) or in vitro (150 ng -12hs) with G-CSF generates low density granulocytes which co-purify with the mononuclear cells in the ficoll® gradient. Moreover, as we had shown in humans, these low density cells, inhibit the production of g-IFN by anti-CD3 activated T cells on flow cytometry studies (17%-T cells alone versus 3% T cells with granulocytes 1:1). Radiation quimaeras were set with (B6 X BALB/c)F1 as hosts reconstituted with T cell depleted C57Bl6 bone marrow, in the presence or absence of nylon wool selected spleen cells (NWSC), as T cell source, from normal or G-CSF treated mice. As previously shown by others, NWSC from G-CSF treated mice diminishes the incidence of acute disease on day 20 post-transplant, from 75 to 25%. In order to investigate if this inhibition was dependent on the activated granulocytes present in the NWSC from G-CSF treated mice, granulocytes were depleted with anti-GR1 and complement. In this case, the incidence of disease is the same or even higher (75% experiment#1 and 100% in experiment #2) than the one observed on the control group (NWSC from control mice). These results strongly suggest that activated granulocytes could indeed inhibit aGVHD. We then generated activated granulocytes in vitro, by treating spleen derived high density granulocytes with 150ng of G-CSF for 12 hs. After the incubation period, a new ficoll® gradient was performed and the low density cells were obtained. T cell contamination on the second gradient was eliminated by anti-CD4 and CD8 complement lysis. These activated granulocytes were inoculated together with NWSC from control mice in the radiation quimaeras at a 1:1 ratio. In this case 100% disease inhibition was observed when compared to the positive control group, where 75% of the animals got sick. Our data indicate that activated granulocytes are the major mediators of the G-CSF immunossupressive effects and that these cells can be used as a novel immune modulator in clinical transplantation to prevent acute GVHD.

scholarly journals Role of accessory cells in B cell activation. III. Cellular analysis of primary immune response deficits in CBA/N mice: presence of an accessory cell-B cell interaction defect.

1980 ◽  
Vol 152 (5) ◽  
pp. 1194-1309 ◽  
Author(s):  
H S Boswell ◽  
M I Nerenberg ◽  
I Scher ◽  
A Singer
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Genetic Defect ◽  
Accessory Cell ◽  
Male Mice ◽  
Accessory Cells ◽  
Antigen Presenting

The effect of the X-linked CBA/N genetic defect on the ability of mice to generate primary responses to thymic-dependent and thymic-independent antigens was assessed by comparing the ability of abnormal (CBA/N x DBA/2)F1 male mice and normal (DBA/2 x CBA/N)F1 male mice to generate 2,4,6-trinitrophenyl (TNP)-specific plaque-forming cell responses to TNP-keyhole limpet hemocyanin (KLH), TNP-conjugated Ficoll (TNP-Ficoll), TNP-Brucella abortus (BA), and TNP-lipopolysaccharide (LPS). The reciprocal F1 combinations used in this study differ genetically only in the origin of their X chromosome, but differ immunologically in that (CBA/N x DBA/2)F1 male mice express all the CBA/N immune abnormalities, whereas (DBA/2 x CBA/N)F1 male mice are immunologically normal. Analysis of thymic-dependent responses to TNP-KLH revealed that abnormal F1 mice were capable of generating primary responses in vivo to high doses of TNP-KLH, but failed to generate responses to suboptimal doses of TNP-KLH that were still immunogenic for normal F1 mice. Furthermore, under limiting in vitro micro-culture conditions, the abnormal F1 mice failed to generate primary thymic-dependent responses to any dose of TNP-KLH, even though under the identical conditions normal F1 mice consistently responded to a wide antigen dose range. The cellular basis of the failure of abnormal F1 mice to respond in vitro to TNP-KLH was investigated by assaying the ability of purified populations of accessory cells, T cells, and B cells from these mice to function in responses to TNP-KLH. The results of these experiments demonstrated that helper T cells and antigen-presenting accessory cells from abnormal F1 mice were competent and functioned as well as the equivalent cell populations from normal F1 mice. Instead, the failure of CBA/N mice to generate primary in vitro responses to TNP-KLH was solely the result of a defect in their B cell population such that B cells from these mice failed to be triggered by competent helper T cells and/or competent accessory cells. Similarly, the failure of abnormal F1 mice to respond either in vivo or in vitro to TNP-Ficoll was not the result of defective accessory cell presentation of TNP-Ficoll, but was the result of the failure of B cells from these mice to be activated by competent TNP-Ficoll-presenting accessory cells. In contrast to the failure of B cells from abnormal F1 mice to be activated in vitro in response to either TNP-KLH or TNP-Ficoll, B cells from abnormal F1 mice were triggered to respond to TNP-BA and TNP-LPS, antigens that did not require accessory cell presentation. The specific failure of B cells fron abnormal F1 mice to be activated in responses that required antigen-presentation by accessory cells suggested the possibility that the X-linked CBA/N genetic defect resulted in B cell populations that might be deficient in their ability to interact with antigen-presenting accessory cells...

scholarly journals Antigen presentation to human T lymphocytes. I. Different requirements for stimulation by hapten-modified cells vs. cell sonicates.

1981 ◽  
Vol 154 (4) ◽  
pp. 1005-1015 ◽  
Author(s):  
S L Abramson ◽  
J M Puck ◽  
R R Rich
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Antigenic Determinants ◽  
Accessory Cell ◽  
Peripheral Blood Mononuclear ◽  
Human T Lymphocytes ◽  
Accessory Cells ◽  
Antigen Presenting ◽  
Unique Ability

We have investigated the cellular and antigenic requirements for incubation of secondary proliferative responses by human T lymphocytes. Two distinct properties of antigen-presenting peripheral blood mononuclear cells were studied: (a) the ability for appropriate cell surface constituents to construct an immunogenic moiety, and (b) the ability to present similar antigenic determinants when they are not covalently bound. Only Ia+ hapten-modified cells were effective stimulators. In contrast, both Ia+ and Ia- cell sonicates could stimulate secondary proliferative responses, but only in the presence of an accessory cell. This accessory cell was present in Ia+ macrophage, but not in Ia+ non-T lymphocyte, preparations. In contrast, macrophages or soluble factors produced by macrophages were not required for primed T cells to undergo hapten-specific proliferation in response to hapten-modified Ia+ stimulator cells. Thus, although all Ia+ cells tested can stimulate primed cells to proliferate, not all Ia+ cells can function as accessory cells for responses to sonicates. This may reflect the unique ability of a subpopulation(s) of Ia+ cells to bind or process sonicates or soluble antigens for appropriate recognition by primed T cells.

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