Ia Antigen Expression Research Articles

Ia Antigen Expression by Human Malignant Lymphomas: Correlation With Conventional Lymphoid Markers

The Ia (p23,30) antigens are useful in determining the B- or T-cell origin of normal peripheral blood lymphocytes. However, exceptions to the preferential B-cell expression of Ia antigens exist, i.e., many plasma cells are Ia– and T cells are rarely Ia+. Therefore, we investigated Ia expression (assayed by direct immunofluorescence using heteroantisera) by cells isolated from 33 malignant lymphomas and 7 benign lymph nodes. This was compared with surface immunoglobulin (SIg) and sheep erythrocyte (SRBC) receptor (E rosette) expression. Results with normal lymph nodes were similar to those described for peripheral blood. Most lymph node B cells were Ia+SIg+. Occasional Ia+SIg– B cells and rare Ia+ T cells were present. Ia antigens were expressed in parallel with SIg in 15 of 19 B-cell lymphomas. In 4 B-cell lymphomas, substantial numbers of neoplastic Ia+SIg– cells were also present, suggesting the presence of neoplastic cells at varying stages of differentiation. Heterogeneity was also seen in those lymphomas associated with monoclonal proteins, as small numbers of Ia+ and Ia– plasma cells were present. Seven cases expressed the T-cell (la–SIg–E+) phenotype. The common acute lymphoblastic leukemia phenotype (Ia+SIg–E–) was rarely expressed and may be uncommon among lymphomas. Three lymphomas expressing the Ia+E+ phenotype were shown to be B-cell malignancies whose SIg had SRBC specificity. One Ia 4 T-cell lymphoproliferative disorder was found. Thus, Ia antigens are useful B-cell markers in most instances. Furthermore, their enumeration allows the demonstration of phenotype heterogeneity in B-cell malignancies, analogous to that described for T-cell malignancies.

HLA Analysis of CD15+ Granulocytes of Leukemic Patients and Assessment of its Implication in Leukemia Immunotherapy

It is of common knowledge that most leukemic patients succumb to infectious complications beside dysfunction in proliferation/differentiation of hematopoietic cells . Recently, it has been shown by several groups that there is a locus specific HLA class I downregulation in the leukemic cells. However, the HLA status of the phenotypically/morphologically normal granulocytes which can cope up with the infectious complications are not known. Therefore it may be worthwhile to study the HLA status in these cell types. We, therefore, investigated the status of HLA-ABC and HLA-DR in the CD15 + granulocytes and observed a higher expression of HLA-DR in several leukemic samples in comparison to normal volunteers (NV). Our data also suggest that only CD15 + granulocytes of myeloid leukemia, a clonal stem cell disorder, have a tendency of decreased HLA class Ia antigen expression. Moreover CD15 + granulocytes of NV showed an enhanced HLA-DR expression in presence of leukemic cells. Interestingly, CD15 + granulocytes collected from normal volunteers were observed to have phagocytic oxidative burst activity towards HLA class Ia downregulated primary leukemic cells. We therefore suggest that neutrophil transplantation may be used for the treatment of leukemia.

Phenotypic characterization of mononuclear inflammatory cells following equine hydroxyapatite/collagen block grafting in rats

To measure the inflammatory changes associated with the implantation of an equine hydroxyapatite and collagen-containing block graft (eHAC block) in a rodent model system, an eHAC block graft was implanted subcutaneously in rats. Control groups included saline, turpentine oil, and human mineralized particulate allograft (hMPA). Animals were sacrificed and tissue samples obtained after three days, as well as after 1, 2, 4 and 8 weeks. A panel of immunologic probes was used to identify circulatory monocytic cells (ED1), resident mononuclear phagocytes (ED2), mononuclear phagocytes of lymphoid origin (ED3), expression of Ia antigen (OX6), T-cells (OX19), and B-cells (OX33). Immunocytochemical localization was performed and mononuclear cells localized with each immunologic probe counted. Rat sera obtained after eight weeks were used for nitrocellulose dot-blotting to assess circulating anti-equine immunoglobulins. Statistical analysis was performed using two-way analysis of variance, in conjunction with the Bonferroni correction to account for multiple comparisons. A transient increase in monocytes at 3 days and 1 week was observed in all groups, but was significantly higher in the turpentine control (P < 0.0001). A significant increase in the numbers of mononuclear cells detected with clones ED2 and ED3 was observed in specimens from the turpentine group, in contrast to the other groups in the 3 day to 4 week interval (P < 0.0001), as well as within all time periods (P < 0.0001). A statistically significant difference in numbers of ED3-positive cells was observed in the hMPA group compared to the saline and the eHAC block groups after one week (P < 0.0001). Significantly more OX6-positive cells were observed in the turpentine group, compared to other groups (3 days to 1 week; P < 0.0001). T-lymphocytes were essentially absent except for rats given turpentine (after 1 week). No B-lymphocyte response was found and none of the rats developed systemic anti-equine antibodies. These data indicate that a cellular immune response is not elicited following implantation with the eHAC block graft, which might serve as an alternative material for regenerative therapy.

Immune privilege and alopecia areata

Hair follicles (HFs) are chiefly characterized by an absent or very low level of expression of MHC class Ia antigens, which is complemented by a number of factors, such as the local production of potent immunosuppressive agents, dysfunction of professional antigen-presenting cells and inhibition of natural killer cell activities. In the hair bulb, immune privilege (IP) is seen only in the anagen stage of HF cycling. The (‘noncycling’) bulge area of human scalp HFs also enjoy some relative, stably maintained IP. Hair bulge IP is constituted not only by factors of HF-IP, but also indoleamine 2,3-dioxygenase and CD200. A collapse of HF (hair bulb and hair bulge) probably plays an important role in the pathogenesis of two of the most common organ-specific autoimmune diseases, alopecia areata and cicatricial alopecia, respectively. Therefore, the therapeutic restoration of IP collapse promises to be a particularly effective future strategy for the treatment of these hair-loss diseases.

Microglia Activated with the Toll-Like Receptor 9 Ligand CpG Attenuate Oligomeric Amyloid β Neurotoxicity in in Vitro and in Vivo Models of Alzheimer’s Disease

Soluble oligomeric amyloid beta (oAbeta) 1-42 causes synaptic dysfunction and neuronal injury in Alzheimer's disease (AD). Although accumulation of microglia around senile plaques is a hallmark of AD pathology, the role of microglia in oAbeta1-42 neurotoxicity is not fully understood. Here, we showed that oAbeta but not fibrillar Abeta was neurotoxic, and microglia activated with unmethylated DNA CpG motif (CpG), a ligand for Toll-like receptor 9, attenuated oAbeta1-42 neurotoxicity in primary neuron-microglia co-cultures. CpG enhanced microglial clearance of oAbeta1-42 and induced higher levels of the antioxidant enzyme heme oxygenase-1 in microglia without producing neurotoxic molecules such as nitric oxide and glutamate. Among subclasses of CpGs, class B and class C activated microglia to promote neuroprotection. Moreover, intracerebroventricular administration of CpG ameliorated both the cognitive impairments induced by oAbeta1-42 and the impairment of associative learning in Tg2576 mouse model of AD. We propose that CpG may be an effective therapeutic strategy for limiting oAbeta1-42 neurotoxicity in AD.

Effect of carbachol on the expression of la on monocyte and lymphocyte apoptosis rate of the burned rats with delayed resuscitation

Objective To explore the changing trend of Ia on monocyte, lymphocyte apoptosis rate, TNF-α and IL-6 in abdominal aorta of burned rats with delayed resuscitation and the influence of application of carbachol on them. Methods Adult male Wistar rats were randomly divided into normal control group(n =8), scald group(n =48) and scald with carbachol treatment group(n =48). In latter two groups, rats were inflicted with 30% total body surface area (TBSA) full-thickness scald and delayed fluid resuscitation. All scald rats were sacrificed at the 6th hours or 1st, 2nd, 3rd, 7th, 14th day after scald, with 8 rats at each time point. Expression of Ia antigen on monocyte and lymphocyte apoptosis rate were determined by direct immunofluorescence on a flow cytometer, and TNF-α and IL-6 was measured by ELISA. Results Expression of la on monocyte was obviously lower than that of controls. The lowest levels were recorded on the 6th hours and 1st day after scald. Subsequently, Ia was elevated gradually, but still lower than that of normal rats(P <0. 01). After administration of carbachol, Ia expression was obviously promoted, compared with the simple scald group (P <0. 01). Lymphocyte apoptosis rate, TNF-α and IL-6 was higher than that of controls(P <0. 01). After administration of cavachol, , lymphocyte apoptosis rate and TNF-α and IL-6 was obviously down-regulated on the 6th hours, 1st day, 2nd day and 3rd day after scald injury, compared with the simple scald group (P < 0. 01 or 0. 05). Conclusion After severe burn with delayed fluid resuscitation, there is a low la expression, high lymphocyte apoptosis rate and increased releasing of proinflammatory cytokine. Immune function was suppressed. Carbacho] could improve the immune function of scald rats with delayed fluid resuscitation. Key words: CarbachoL/PD ; Bums/DT/IM

Suppression of experimental allergic encephalomyelitis by intraventricular administration of interferon-gamma in Lewis rats

Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS) which causes paralysis. Several studies have reported the involvement of Ia antigen-expressing cells in the pathogenesis of EAE. Interferon-gamma (IFN-gamma) can induce Ia antigen expression on a wide range of cells. We examined the effect of IFN-gamma on EAE in Lewis rats. Systemically administered IFN-gamma did not change the disease course of EAE, whereas IFN-gamma applied locally into the ventricular system of the CNS resulted in complete suppression of clinical signs. Furthermore, we found that systemic administration of anti-IFN-gamma just prior to the onset of clinical symptoms resulted in a more severe disease course. We conclude that IFN-gamma is capable of exerting a suppressive action in EAE, possibly through induction of Ia antigen expression or through the induction of suppressive mechanisms locally in the CNS.

Regional cellular responses to intraperitoneal infection.

Leucocytes in different body compartments were examined in a murine intra-abdominal abscess model: (i) peripheral blood; (ii) peritoneal exudate; (iii) abscess wall; and (iv) abscess pus, with respect to their phagocytic ability, CR3 expression and Ia antigen expression (murine MHC antigen). The ability of serum or supernatant in each compartment to opsonize Staphylococcus aureus was also determined. Mice responded to caecal ligation and puncture (CLP) with systemic monocytosis, an increased amount of opsonins in peritoneal fluid and an increased phagocytosis in pus leucocytes. This increased phagocytic ability and CR3 expression both subsequently decreased. Monocyte/macrophage Ia expression was reduced in all measured compartments over time. In contrast, sham-operated animals, without an intra-abdominal abscess, responded to operation with an even greater increase in peritoneal exudate phagocytic ability and in monocyte/macrophage Ia expression in all compartments which was sustained beyond 1 week. Decreased peritoneal exudate cell and peripheral blood Ia was still present after 28 days in CLP animals, compared with both sham and normal animals (P less than 0.05, P less than 0.02, respectively). For all parameters, changes observed in peripheral blood did not reflect those present near the site of infection. Proper understanding of local or regional infection must take into account and ultimately alter these generally unappreciated changes in and about the actual site of infection.

Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis

Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M-PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/- 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation.

Modulation of murine host-versus-graft disease by anti-CD3 monoclonal antibody

BALB/c mice made tolerant to A/J alloantigens by neonatal injection of (A/J x BALB/c)F1 spleen cells develop a host-versus-graft (HVG) disease due to the activation of donor B cells by a subset of host alloreactive helper T cells. We have investigated the effects of a single neonatal injection of the 145-2C11 anti-mouse CD3 monoclonal antibody (MoAb) on the establishment of allotolerance and on the development of the immunopathological features of HVG disease. First, this treatment did not modify the specific anti-donor cytotoxic T lymphocyte (CTL) unresponsiveness or the persistence of circulating immunoglobulins bearing donor allotype. Second, the hyper IgE, the hyper IgG1 and the increased expression of Ia antigens on B cells found in untreated HVG mice were not observed after injection of the 145-2C11 MoAb. Likewise, treated mice displayed lower levels of anti-DNA IgG antibodies and less glomerular immune deposits as compared with untreated HVG mice. We conclude that the administration of the anti-CD3 MoAb did not interfere with the induction of allotolerance but exerts a pronounced inhibitory effect on the associated immunopathological syndrome.

Etiology of sperm immunity in women

Sperm immunity in females can reduce the likelihood of natural conception, and sperm antibodies from female sera have been shown to inhibit IVF in humans and in several animal models. The etiology of sperm immunity in human females is unknown, but several possible mechanisms have been proposed, including cross-reactivity with microbial antigens and interferon gamma-mediated potentiation of the antisperm immune response in women whose male partners have sperm autoantibodies in their semen. This article reviews these ideas and postulates a novel hypothesis based on the potential for the generation of anti-idiotype antibodies in women whose partners have sperm antibodies in their semen.

Organic extract of diesel exhaust particles stimulates expression of Ia and costimulatory molecules associated with antigen presentation in rat peripheral blood monocytes but not in alveolar macrophages

We hypothesized that diesel exhaust particles (DEP) induce the activation of antigen-presenting cells (APC) in lung. The present study was designed to clarify the following about DEP: (1) whether it affects the expression of Ia and B7 molecules in alveolar macrophages (AM) as a mature cell or in peripheral blood monocytes (PBM) as an immature cell, (2) if it affects the antigen-presenting (AP) activity of PBM, (3) what component of DEP is responsible for the effects, and (4) whether the effect of DEP is related to oxidative stress. DEP was extracted with methylene chloride. Cells were exposed to whole DEP, organic extract, or residual particles for 24 h. Cell-surface molecules were measured by flow cytometry. AP activity was assessed by antigen-specific T cell proliferation. Whole DEP or organic extract significantly increased the expression of Ia and B7 molecules on PBM but not on AM. No significant effect of residual particles was observed. A low concentration of organic extract also increased the AP activity of PBM. When the induction of an antioxidative enzyme was assessed, heme oxygenase-1 protein was found to be significantly increased by exposure to whole DEP, and the organic extract was more effective than the residual particles. Furthermore, the organic extract-induced expression of Ia antigen on PBM was reduced by the addition of an antioxidative agent. These results suggest that DEP may act on immature APC and enhance their AP activity and that the action contributing to oxidative stress may be mediated by organic compounds of DEP.

Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages engineered to produce IFNgamma: an approach for gene therapy.

Macrophage (Mphi)-based vectors are highly mobile cellular shuttles designed to deliver therapeutic genes within the tissues. We engineered a mouse Mphi cell line to express the murine interferon-gamma (IFNgamma) under the control of an inducible promoter containing the hypoxia-responsive element, which can be triggered by hypoxia and other stimuli. We show that this Mphi vector can be induced to produce IFNgamma under normoxic conditions by stimulation with picolinic acid (PA), a catabolite of tryptophan, or desferrioxamine (DFX), an iron-chelating drug. The Mphi vector responds to IFNgamma with the induction of IRF-1 and of other IFNgamma-inducible genes, the expression of Ia antigens and induction of phagocytic activity. Inducible nitric oxygen synthase gene expression, nitric oxide production, as well as TNFalpha secretion were enhanced by PA or DFX as the sole stimuli. None of the above responses could be triggered individually by PA or DFX in control, normal Mphi, indicating that the Mphi vector overcame the need for costimulatory molecules derived from the immune system for its full activation. Furthermore, we demonstrate that extracellular iron can downregulate such response, thereby identifying an additional tool for the fine tuning of the Mphi vector response to stimulation.

Regulation of major histocompatibility complex class II gene expression in trophoblast cells

Trophoblast cells are unique because they are one of the few mammalian cell types that do not express major histocompatibility complex (MHC) class II antigens, either constitutively or after exposure to IFN-γ. The absence of MHC class II antigen expression on trophoblast cells has been postulated to be one of the essential mechanisms by which the semi-allogeneic fetus evades immune rejection reactions by the maternal immune system. Consistent with this hypothesis, trophoblast cells from the placentas of women suffering from chronic inflammation of unknown etiology and spontaneous recurrent miscarriages have been reported to aberrantly express MHC class II antigens. The lack of MHC class II antigen expression on trophoblast cells is due to silencing of expression of the class II transactivator (CIITA), a transacting factor that is essential for constitutive and IFN-γ-inducible MHC class II gene transcription. Transfection of trophoblast cells with CIITA expression vectors activates both MHC class II and class Ia antigen expression, which confers on trophoblast cells both the ability to activate helper T cells, and sensitivity to lysis by cytotoxic T lymphocytes. Collectively, these studies strongly suggest that stringent silencing of CIITA (and therefore MHC class II) gene expression in trophoblast cells is critical for the prevention of immune rejection responses against the fetus by the maternal immune system. The focus of this review is to summarize studies examining the novel mechanisms by which CIITA is silenced in trophoblast cells. The elucidation of the silencing of CIITA in trophoblast cells may shed light on how the semi-allogeneic fetus evades immune rejection by the maternal immune system during pregnancy.

The Hair Follicle and Immune Privilege

This essay reviews the available evidence that the proximal hair follicle epithelium generates and maintains an area of relative immune privilege during a defined segment of the hair cycle (i.e., during anagen). This immune privilege is chiefly characterized by a very low level of expression of MHC class Ia antigens and by the local production of potent immunosuppressive agents, such as alpha-MSH and TGF-beta1. We discuss the putative functions of immune privilige of the anagen hair bulb, favoring the view that immune privilege serves mainly to sequester anagen- and/or melanogenesis-associated autoantigens from immune recognition by autoreactive CD8+ T cells. On this basis, we develop how the "immune privilege collapse model" of alopecia areata pathogenesis was conceived. In our discussion of the clinical implications of immune privilege, we outline the currently available evidence in support of this still hypothetical scenario to explain the initiation, progression, and termination of alopecia areata lesions. We review the most recent evidence from our laboratory that alpha-MSH, IGF-1, and TGF-beta1 can downregulate IFN-gamma-induced ectopic MHC class I expression in human anagen hair bulbs in vitro. Finally, we suggest that hair follicle-derived alpha-MSH, IGF-gamma, and TGF-beta1 form part of a constitutively active "IP restoration machinery" of the anagen hair bulb, which we propose to be recruited whenever the hair follicle suffers immune injury. Finally, we sketch some particularly promising avenues for future investigation into the far too long ignored hair follicle immune privilege.

Cellular inflammatory response to porcine collagen membranes.

The purpose of this study was to assess local inflammatory changes associated with the implantation of three different porcine collagen membranes having potential use in periodontal regeneration. Materials were implanted subcutaneously into prepared sites along the dorsal skin surface of 60 female Wistar rats. Saline and turpentine were used as negative and positive controls, respectively. Animals were killed and biopsies obtained after 3 d, and at 1, 2, 4, 6, and 8 weeks after membrane implantation. A panel of six monoclonal antibodies was used to identify circulating monocytes (ED1), resident tissue macrophages (ED2), lymphoid macrophages (ED3), Ia-antigen expression (OX6), T-lymphocytes (OX19), and B-lymphocytes (OX33). Cells identified by each antibody were subjected to quantitative immunocytochemistry to compare any differences present among groups. Sera obtained 8 weeks after grafting were used in immunoblotting assays to detect the presence of systemic antiporcine antibodies. We found that the mononuclear cell subsets associated with implantation of porcine collagen membranes were similar to those obtained with saline administration. On the other hand, the use of turpentine resulted in an inflammatory infiltrate characterized by significantly higher numbers of all six monoclonal cell subsets at all time periods evaluated, compared to either saline or any of the membranes (P < 0.001). The collagen membranes do not appear to be associated with a significant local inflammatory response, nor a systemic immune response, and thus appear to be well tolerated, rendering them useful in periodontal regeneration.

Altered Pattern of Major Histocompatibility Complex Expression in Renal Carcinoma: Tumor-Specific Expression of the Nonclassical Human Leukocyte Antigen-G Molecule Is Restricted to Clear Cell Carcinoma While Up-Regulation of Other Major Histocompatibility Complex Antigens Is Primarily Distributed in All Subtypes of Renal Carcinoma

Renal epithelial cancers represent a heterogeneous group of neoplasms arising from the malignant transformation of presumed diverse cell lineages. We recently demonstrated that tumor-specific up-regulation of human leukocyte antigen (HLA)-G, a nonclassical HLA class Ib molecule that might be involved in immune evasion by tumor cells, frequently occurs in conventional (clear cell) renal carcinoma. We here examined whether HLA-G activation is a common process affecting all types of renal epithelial tumors. We analyzed a series of 38 paraffin-embedded tumors including clear cell, papillary, chromophobe, collecting duct carcinoma, and oncocytoma. Seven of 12 (58%) clear cell tumors were positive by immunohistochemistry, whereas all of the other subtypes of renal carcinoma were negative for HLA-G expression. Developing or adult normal renal tissue were devoid of HLA-G expression. We also observed that ectopic expression of HLA class II antigens occurs more frequently in clear cell renal carcinoma than in other subtypes of renal tumors. Moreover, in contrast to the common observation of a down-regulation of major histocompatibility complex class Ia antigens reported in various tumors, the concomitant study of the same biopsies for classical HLA class Ia antigen expression revealed a general increase of HLA class Ia expression, regardless of histological subtypes. These results provide evidence for the heterogeneity of major histocompatibility complex expression patterns in renal carcinoma and support the hypothesis that specific mechanisms underlying the malignant transformation into clear cell renal carcinoma up-regulate expression of HLA-G and to a lesser extent HLA class II molecule expression. Considering the immunotolerant role of HLA-G toward the immune response, these mechanisms may thus provide renal cell carcinoma tumor cells with additional means to escape immune surveillance.

Ozone exposure enhances expression of cell-surface molecules associated with antigen-presenting activity on bronchoalveolar lavage cells in rats.

In this study, we investigated the effects of ozone (O3) exposure on expression of cell-surface molecules associated with antigen presentation and on accessory activity of bronchoalveolar lavage cells (BAL cells). Rats were exposed to 1 ppm O3 for 3 days. Expression of cell-surface molecules was measured by flow cytometry. Accessory activity of BAL cells was assessed by the allogeneic mixed lymphocyte reaction (MLR) and specific antigen-presenting activity. O3 exposure increased the expression of Ia, B7.1, B7.2, and CD11b/c on BAL cells. Morphological and immunological studies showed the Ia-positive cells to have monocyte-like features. Peripheral blood monocytes expressed Ia, B7.1, B7.2, and CD11b/c. The Ia expression on the monocytes was further increased by treatment of them with BAL fluid from O3-exposed rats (O3-BALF). Resident alveolar macrophages, however, did not express Ia antigen, and the Ia expression was not increased by O3-BALF. Neutrophils, which also infiltrated in response to O3 exposure, did not express Ia, B7.1, and B7.2. Therefore, infiltrating monocytes may have caused the increased expression of Ia and B7 molecules on BAL cells exposed to O3. The accessory activity of BAL cells in terms of MLR and specific antigen-presenting activity was also enhanced by O3 exposure. The present study suggests that monocytes infiltrating in response to O3 exposure caused enhancements of the expression of Ia and costimulatory molecules on and the accessory activity of BAL cells.

Acute cytokine response to systemic adenoviral vectors in mice is mediated by dendritic cells and macrophages.

We investigated the cellular basis for secretion of inflammatory cytokines in mice following intravenous administration of adenoviral vectors (Ad). Serum inflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-alpha (TNF-alpha) were detected as early as 6 h following intravenous injection of Ad-expressing Escherichia coli beta-galactosidase (Ad-lacZ). Ad-lacZ readily accumulated in the splenic marginal zone 1 h after intravenous infusion, where both dendritic cells (DCs) and macrophages were transduced and activated within 6 h. Flow cytometric analyses showed that the expression of Ia and CD86 antigens was markedly enhanced on splenic DCs indicating their activation in vivo by Ad-lacZ. Upon ex vivo culture, these early-activated splenic DCs spontaneously produced high levels of IL-6 and IL-12. By contrast, activated splenic macrophages spontaneously secreted only IL-6. Elimination of tissue macrophages and splenic DCs in vivo considerably reduced the early release of IL-12, IL-6, and TNF-alpha and significantly blocked the specific cellular immune response to Ad and the transgene product in vivo. Our findings indicate that preferential activation of DCs and macrophages may account for Ad-triggered acute inflammatory response in vivo in mice. Moreover, DCs and macrophages may play different roles in this process in terms of their abilities to produce distinct patterns of inflammatory cytokines.

Fluorescent granular cells of the thymus can be identified as dendritic macrophages.

Fluorescent granular cells of the thymus lobule containing neurotransmitter monoamines express Ia antigen and S-100 protein, which attests to their macrophage origin; positive staining with aldehyde fuchsin points to secretion of peptide hormones by these cells. These facts and the absence of phagocytic activity allow to identify these cells as dendritic macrophages.