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Published online before print June 24, 2004
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Departments of Respiratory and Critical Care Medicine, First Affiliated Hospital, Guangxi Medical University, People’s Republic of China
1 Correspondence: Departments of Respiratory and Critical Care Medicine, First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, P. R. China. E-mail: hzshi{at}tom.com
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONEOSINOPHILS EXPRESS CLASS II...EOSINOPHILS PRESENT ANTIGEN IN...AIRWAY EOSINOPHILS PRESENT...ANTIGEN PRESENTATION OF...REFERENCES |
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Key Words: lymphocytes • antigen • airway • Th1/Th2
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONEOSINOPHILS EXPRESS CLASS II...EOSINOPHILS PRESENT ANTIGEN IN...AIRWAY EOSINOPHILS PRESENT...ANTIGEN PRESENTATION OF...REFERENCES |
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-I [5
] or CD40 [6
], found on eosinophils from allergic subjects. Other cytokines or tissue or extracellular matrix-derived, activating stimuli are likely to be involved as well in augmenting specific functional capabilities of eosinophils [7
]. Allergen-induced recruitment of eosinophils into lung tissues is correlated with roles of CD4+ T cells, presumably Th2 cells, and cytokines released by such T cells [8 9 10 ]. In humans, IL-4 and IL-5 are functionally important in causing eosinophil infiltration into the airway and its activation as well as airway hyper-responsiveness to methacholine [11 , 12 ]. The accumulation of eosinophils in tissues, as in chronic asthma or following acute challenges in the lungs, correlates with measures of local T cell activation. For instance, increases in activated T cells, eosinophils, and cytokine mRNA expression for IL-5 and GM-CSF have been documented in bronchial biopsies after allergen inhalation challenge in atopic asthmatics [13 ]. Thus, there has been an increasing recognition that eosinophil accumulation and enhanced effector functions at tissue sites of allergic reactions may be intimately related to lymphocyte activation, especially by Th2-like lymphocytes elaborating cytokines, including IL-5 and GM-CSF, which prolong the viability and enhance the effector responses of mature eosinophils.
Although there has been an increasing recognition of the roles of lymphocytes in the pathogenesis of allergic reactions and the regulation of eosinophil involvement in such reactions, there should be collaborative interactions existing between lymphocytes and eosinophils in respiratory tract tissue environments. If eosinophils function to help regulate lymphocyte responses to aeroallergens encountered in the respiratory tract, such functions may be "beneficial" in normal mucosal-immune responses and deleterious in contributing to sustaining or propagating allergic reactions within the airways.
Studies in the 1960s documented a remarkable capacity of eosinophils to internalize administered antigen to rapidly traffic to regional lymph nodes. Primary injection of varied antigen (3H- or fluorescently labeled) into the footpads of mice or guinea pigs was followed by antigen uptake within eosinophils. Within 1 h of antigen injection, eosinophils containing the labeled antigens localized within regional lymph nodes [14 , 15 ]. Uptake of antigen preferentially into eosinophils was even greater when antibody to the antigen was present [16 ]. Moreover, repeated administration of antigen leads to even greater localization of antigen-containing eosinophils in draining lymph nodes [17 ]. Although these findings by themselves do not establish that eosinophils were serving as antigen-presenting cells (APCs), these experiments do document roles for eosinophils in the very early uptake of antigen, do indicate a role for antibody-facilitated uptake of antigen by eosinophils, as antibody-facilitated uptake of antigen is now recognized to enhance APC function, and do suggest that eosinophils exhibit specific integrin-based or other mechanisms for preferential localization within lymph nodes.
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EOSINOPHILS EXPRESS CLASS II MAJOR HISTOCOMPATIBILITY COMPLEX (MHC-II) AND COSTIMULATORY MOLECULES |
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TOPABSTRACTINTRODUCTIONEOSINOPHILS EXPRESS CLASS II...EOSINOPHILS PRESENT ANTIGEN IN...AIRWAY EOSINOPHILS PRESENT...ANTIGEN PRESENTATION OF...REFERENCES |
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For eosinophils to function as APCs, they must express MHC-II proteins [human leukocyte antigen (HLA)-DR]. Blood eosinophils from most normal and eosinophilic donors do not express MHC-II proteins, even if these eosinophils appear phenotypically activated [24
], but when blood-derived human eosinophils are cultured in vitro with specific cytokines, including IL-3, IL-4, GM-CSF, and interferon-
(IFN-), these eosinophils are uniformly induced to synthesize and express HLA-DR [24
25
26
]. In addition, transendothelial migration of eosinophils, as would occur when eosinophils are recruited to leave the bloodstream and enter tissues, increases their HLA-DR expression [27
]. Thus, human, mature eosinophils have the capacity to express HLA-DR.
Numerous studies have established that airway eosinophils express HLA-DR. Eosinophils in the sputum of asthmatics express HLA-DR [28 ], as do airway but not blood eosinophils in chronic eosinophilic pneumonia [29 , 30 ]. In patients with asthma, even blood eosinophils have been found to express greater HLA-DR than eosinophils from normal subjects [31 ]. Moreover, bronchoalveolar lavage eosinophils, obtained 48 h after segmental antigen [32 ] or 4–6 h after inhalation [33 ] challenge in allergic subjects, exhibited HLA-DR expression, which was absent from blood eosinophils. Thus, the recruitment and activation of eosinophils into the airways elicited by allergen challenge lead to the induction of HLA-DR expression on the recruited airway eosinophils [32 , 33 ]. Levels of MHC-II protein expression need be only low (210–340/cell) for a cell to function as an APC [34 ]. Levels of HLA-DR fully sufficient for APC function are present on airway eosinophils in the sputum or airway lavages from allergic subjects.
To present antigen, eosinophils should provide costimulatory signals for lymphocytes. CD40, a type I integral surface membrane glycoprotein, is a member of the nerve growth factor/tumor necrosis factor receptor superfamily [35 ]. CD40 is also found on B cells, dendritic cells (DCs), thymic epithelial cells, monocytes, and endothelial cells. Cross-linking CD40 on DCs has increased their survival, altered their morphology, induced cytokine secretion, and increased cell-surface expression of HLA-DR, CD25, CD58, CD80, and CD86 [36 ]. CD40 preferentially costimulates activation of CD4+ cells through its natural ligand CD40 ligand. CD40–CD40 ligand interaction in vivo is involved in the activation and proliferation of eosinophils and mast cells associated with Th2 responses [37 ] and experimental allergic inflammation in the airways of mice [38 ]. It had been reported that eosinophils can express CD40, which is present on blood eosinophils freshly isolated from certain notable, allergic donors [6 ]. In nasal polyp tissues, lesional eosinophils are the dominant cell type expressing CD40 [6 ]. Human eosinophils almost uniformly contain abundant CD40 but vary in the levels of CD40 expressed on the outer plasma membrane with expression enhanced on eosinophils from atopic subjects. Further study confirmed that CD40 on eosinophils was responsible for providing costimulation to anti-CD3-activated T cells.
As B7 molecules CD80 and CD86 and related B7 homologs are especially significant on APCs for delivering requisite costimulatory signals to lymphocytes, B7 molecules on eosinophils have been well studied. Woerly and co-workers [39 ] have reported that eosinophils from patients with allergic and other eosinophilic disorders can express CD86 but not CD80, as well as more typically found on T cells. Celestin and co-workers [40 ] have also reported that populations of highly pure eosinophils, freshly isolated from the blood of normal subjects, expressed no detectable CD80 and CD86 molecules on their surface. Following culture with 20 ng/ml IL-3, surface CD86 expression became consistently detectable at 48 h and further increased at 72 h. In contrast to its induction of CD86, IL-3 failed to induce expression of CD80 on eosinophils.
Eosinophils purified from peritoneal exudate cells of IL-5-transgenic mice express CD80 and CD86 without cytokine treatment, and the expression of these two molecules on the eosinophils is increased by incubation with GM-CSF [41 ]. We determined previously whether murine eosinophils from the airways of antigen-sensitized and -challenged mice expressed molecules potentially involved in presentation of exogenous antigens. Although peritoneal eosinophils from IL-5-transgenic mice did not express MHC II proteins, airway eosinophils recovered from antigen-sensitized and -challenged BALB/c mice expressed high levels of I-Ad expression. These airway eosinophils, like peritoneal eosinophils from IL-5-transgenic mice [41 ], also expressed high levels of CD80 and CD86 [42 ]. An inability to recover eosinophils in sufficient numbers from normal mice precluded determining whether the expression of these proteins was constitutive on murine eosinophils or induced or enhanced following antigen sensitization and challenge.
In addition to cell-surface proteins involved in cognate APC-lymphocyte costimulatory interaction, APCs can provide cytokines that promote APC function or potentially act on responding T cells to bias toward Th2 or Th1 responses. Human eosinophils elaborate lymphocyte chemoattractant activity that is largely mediated by IL-16 and regulated on activation, normal T cell expressed and secreted (RANTES) [43 ]. IL-16, which attracts CD4+ cells, and RANTES are preformed in eosinophils [43 ]. With a novel, solid-phase, dual antibody capture and immunoflurescent detection microscopic assay (the EliCell assay), Bandeira-Melo and co-workers [44 ] have shown that RANTES is rapidly releasable from eosinophils by selective, noncytolytic vesicular transport. Bandeira-Melo and co-workers [45 ] have also reported that eosinophils are sources of IL-4. As IL-4 contributes to the polarization toward Th2 differentiation, its release from eosinophils may contribute their APC functions by enhancing Th2 development.
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EOSINOPHILS PRESENT ANTIGEN IN VITRO |
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mRNA, detectable by Northern blot hybridization and in situ hybridization, and expressed IL-1 protein detectable by immunohistochemistry. These findings indicate that human eosinophils can process antigen, express the costimulatory cytokine IL-1, and after cytokine-elicited induction of HLA-DR expression, can function as HLA-DR-dependent, MHC-restricted APCs in stimulating T lymphocyte responses [25
]. Mawhorter and co-workers’ works [46
] confirmed that GM-CSF-treated eosinophils induced resting T cells to proliferate in response to the Staphylococcal superantigens, Staphylococcus enterotoxins A, B, and E. Furthermore, superantigen-induced T cell proliferation correlated with the proportion of eosinophils expressing MHC-II molecules. When eosinophils and macrophages were compared for their ability to act as accessory cells for superantigen induced T cell proliferation, macrophages were more efficient than eosinophils, which were not effective APCs for microbial antigens. Proliferative responses to purified protein derivative, tetanus toxoid, or Brugia malayi antigen were observed in only three of nine eosinophils studies. The three positive studies included activated CD4+ cells, whereas no responses were observed with resting CD4+ cells. Macrophages and mononuclear cells were effective APCs for these antigens for resting and activated CD4+ cells [46
]. These data indicate that although MHC-II-expressing eosinophils can serve as APCs, they are relatively inefficient for the activation of CD4+ cells by microbial antigen, which requires processing. It is well known that IL-5 is particularly important for the terminal differentiation of committed eosinophil precursors [47 ]. IL-5 activates mature eosinophils and prolongs their survival in culture, possibly via its ability to delay apoptosis [48 , 49 ], as well as selectively enhancing eosinophils degranulation, antibody-dependent cytotoxicity, and adhesion to vascular endothelium [50 , 51 ]. More recently, we have demonstrated that the eosinophil-related T cell proliferation could be enhanced significantly by IL-5, and the soluble fusion protein, CTLA-4-immunoglobulin (Ig), inhibited eosinophils to present antigen to T cells despite whether IL-5 was used (our unpublished data). It could be concluded that IL-5 enhanced the ability of eosinophils to present antigen, possibly by increasing the expression of B7 molecules on eosinophils, as CTLA-4-Ig, very potently and specifically, inhibits costimulation between APC CD80/CD86 and T cell CD28 or CTLA-4 [52 ].
Episodes of virus-induced exacerbations of asthma are accompanied by increased eosinophils in respiratory secretions and evidence of eosinophil degranulation. Although rhinoviruses are the viruses most often implicated in exacerbations of asthma in children and adults, little is known about the immune response to this group of viruses and in particular, eosinophil-rhinovirus interactions. To define such interactions, Handzel and co-workers [53
] incubated human rhinovirus-16, a serotype using intracellular adhesion molecule-1 as a receptor, with eosinophil purified from peripheral blood and measured eosinophil-rhinovirus-binding, eosinophil-mediated antigen presentation and T cell activation, and eosinophil cell-surface marker expression and superoxide production. Significant rhinovirus-16-binding occurred to eosinophils that were pretreated with GM-CSF, and this binding was inhibited by anti-intracellular adhesion molecule-1 mAb. Eosinophils also presented viral antigens to rhinovirus-16-specific T cells, causing T cell proliferation and secretion of IFN-. Rhinovirus-16 induced a significant shift from CD18dim to CD18bright but did not affect eosinophil expression of CD54, CD69, or HLA-DR. Finally, rhinovirus-16 did not induce superoxide production from peripheral blood eosinophils [53
]. These findings suggest that rhinovirus-16 also binds to airway eosinophils, which resemble GM-CSF-treated blood eosinophil in terms of high expression of intracellular adhesion molecule-1. Furthermore, eosinophils could participate in rhinovirus-induced immune responses through antigen presentation and T cell activation. By activating rhinovirus-specific T cells, eosinophils may play an important role in the initiation of antiviral T cell responses, and these effects could also contribute to enhanced airway inflammation and increased asthma symptoms in susceptible individuals.
Del Pozo and co-workers [54 ] have studied the role of murine eosinophils as APCs, and they have obtained several T cell clones specific for Mesocestoides corti antigens and used T cell hybridoma specific for ovalbumin to observe the APC function of murine eosinophils. GM-CSF-activated, pure eosinophils are able to present M. corti antigens to specific T cell clones or ovalbumin to T cell hybridoma 3DO 11.10, inducing the proliferation of T cell clones and IL-2 release by the T cell hybridoma. Proliferation of T cells clones is dependent on the number of eosinophils used as APCs. Lysosomotropic agents, such as chloroquine and ammonium chloride, which inhibit antigen processing, impaired eosinophil presentation.
We have assessed the capacity of eosinophils recruited into the luminal airways by aerosol antigen challenge to process the antigen to which they were exposed within the airways [42 ]. Highly purified, splenic T cells from ovalbumin-immunized mice were cultured with increasing numbers of eosinophils isolated and purified from the airways of mice challenged with aerosolized ovalbumin. The addition of eosinophils exposed to ovalbumin in vivo yielded an eosinophil dose-dependent increase in T cell proliferation, compatible with eosinophils presenting processed ovalbumin peptides to the sensitized T cells. The addition of exogenous antigen to these eosinophil-T cell cocultures yielded even greater eosinophil dose-dependent proliferation, indicative that eosinophils in vitro were further serving as APCs. To ascertain that the heightened T cell proliferation seen with eosinophils exposed in vivo to antigen was not attributable to a mitogenic or other antigen-independent, stimulatory process, the antigen specificity of the eosinophil antigen-presenting function was evaluated. Our findings showed that eosinophils were the only APCs present in these cultures with purified and antigen-specific T cells, demonstrated by the failure of T cells to proliferate in response to exogenous antigens in the absence of eosinophils. Again, eosinophils exhibited antigen-specific antigen-presenting capability in response to exogenous antigen added during T cell proliferation assays, as well as their capacity to process and present antigen to which they were exposed in vivo within the airways. To further evaluate whether eosinophils were providing requisite B7 costimulatory signals for their APC function [55 ], we also assessed the roles of CD80 and CD86 as costimulatory signals in eosinophil antigen presentation to ovalbumin-sensitized T cells in vitro. It was found that anti-CD80 and anti-CD86 mAb partially blocked proliferation responses; a combination of anti-CD80 and anti-CD86-blocking mAb and CTLA-4-Ig yielded even greater inhibition of eosinophil-elicited T cell proliferation [42 ]. Therefore, the inhalational exposures of murine airway eosinophils to antigens were shown to be sufficient for these airway eosinophils, by antigen-specific and CD80- and CD86-dependent means, to present antigens to T cells in in vitro assays. These findings using in vivo exposures of eosinophils to antigens solely within the airways extend prior studies demonstrating that murine [41 , 54 ] and human [25 , 46 , 56 , 57 ] eosinophils exposed to antigens in vitro may serve as APCs.
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AIRWAY EOSINOPHILS PRESENT ANTIGEN IN VIVO |
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It is conventionally assumed that eosinophil transit through the airway epithelium into the lumen is a terminal event. To evaluate the capacity of eosinophils within the tracheobronchial lumen to enter tissues, eosinophils, recovered from the airways of antigen-sensitized mice following aerosol airway challenges, were fluorescently labeled ex vivo with 1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [3
] and instilled into the tracheas of normal mice. By 8 h after tracheal instillation, labeled eosinophils were visible in the subcapsular region and streaming through the subcapsular sinus. With increasing time, the numbers of eosinophils entering the regional lymph nodes increased, peaking at 24 h and persisting for at least 120 h. By 24 h after instillation, labeled eosinophils were located predominantly in the T cell regions of lymph nodes, with only occasional eosinophils in the B cell areas or the subcapsular sinus [42
]. Although intraluminal eosinophils clearly enter peritracheal tissues and traffic to lymph nodes, the route and mechanisms of this migration are not yet defined. A recent study in an analogous murine model of asthma demonstrated that ovalbumin-sensitized and ovalbumin airways-challenged mice exhibited eosinophil accumulations in the airways, peritracheal tissues, and especially into peritracheal lymph nodes [60
]. Whereas the lymph node localization of eosinophils in that study was in the context of endogenous eosinophil accumulations in the entire airways tissues following inhalational challenge in sensitized mice, our studies demonstrate that exogenous, fluorescent-labeled eosinophils introduced specifically into the tracheobronchial lumina of normal mice exhibit homing to peritracheal lymph nodes [42
]. A candidate mechanism whereby endobronchial eosinophils home to regional lymph nodes might involve signaling of eosinophils by eotaxin or other chemokines. With confluent intestinal epithelial monolayers, eosinophils can traffic in both directions across the epithelium [61
]. The capacity of the airway epithelium to produce cytokines and chemokines active in eliciting eosinophil migration, such as IL-16 [62
], RANTES [63
, 64
], and eotaxin [65
], has usually been considered in the context of their directing eosinophil migration into the lumen of the airways. Alternatively, these epithelium-expressed chemoattractants might function to recruit at least some eosinophils from the lumen back toward the epithelium. As RANTES has been shown to be released specifically in a polarized manner at the apical surface of airway epithelial cells, this apical expression of RANTES is even more prominent in the airways of asthmatics [64
]. Hence, for this eosinophil chemotactic chemokine, there would be a concentration gradient within the lumen increasing toward the apical surface of the epithelium, which might direct eosinophil migration from the lumen. Therefore, we assessed whether the migration of eosinophils from the airway lumen to regional lymph nodes was governed by eotaxin expressed in normal recipient mice. The migration of eosinophils obtained following aerosol antigen challenge of mice with genetic deletion of the chemokine receptor (CCR)3 for eotaxin (and related chemokines) was examined. CCR3–/– eosinophils exhibited identical homing to CCR3+/+ eosinophils from wild-type mice. This mechanism, however, based on chemokines, such as eotaxin, which signal eosinophils via the CCR3, is not likely to be involved. Eosinophils lacking the CCR3 homed identically to peritracheal lymph nodes. Whether other chemokine attractants or eosinophil-expressed integrins, such as 4ß7 [66
], may be involved in the localization of eosinophils to peritracheal lymph nodes remains to be established.
Many cell types have the capacity to serve as APCs. Thus, for eosinophils, a critical test was to ascertain whether eosinophils within the airways, after encountering inhaled antigens, could function to present antigens and elicit T cell responses in vivo. Our studies established not only that endotracheal eosinophils homed to T cell-rich regions of draining peritracheal lymph nodes but also that these antigen-exposed, airway-derived eosinophils, when instilled into the airways of antigen-sensitized mice, were capable of stimulating T cell-proliferative responses in vivo within draining peritracheal lymph nodes. These eosinophil-mediated in vivo T cell-proliferative responses were antigen-specific, CD80/CD86-dependent, and limited to CD4+ T cells [42 ]. In a more recent study, van Rijt and colleagues [67 ] have investigated whether eosinophils are capable of presenting antigen to unprimed T cells in draining lymph nodes of the lung and compared this capacity with professional DCs. During development of eosinophilic airway inflammation in ovalbumin-sensitized and -challenged mice, CCR3+ eosinophils accumulated in the draining lymph nodes. To study their function, eosinophils were isolated from the bronchoalveolar lavage fluid of mice by sorting on CCR3+B220–CD3–CD11cdim low, autofluorescent cells, avoiding contamination with other APCs, and were injected intratracheally into mice that previously received fluorescent-labeled ovalbumin T cell receptor-transgenic T cells. Eosinophils did not induce divisions of T cells in the draining lymph nodes, whereas DCs induced on average 3.7 divisions in 45.7% of T cells. To circumvent the need for antigen processing or migration in vivo, eosinophils were pulsed with ovalbumin peptide and were still not able to induce T cell priming in vitro, whereas DCs induced vigorous proliferation. This investigation does not support any role for airway eosinophils as APCs to naive T cells, despite their migration to the draining lymph nodes at times of allergen exposure and antigen presentation to sensitized T cells.
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ANTIGEN PRESENTATION OF EOSINOPHILS AND TH1/TH2 IMBALANCE |
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TOPABSTRACTINTRODUCTIONEOSINOPHILS EXPRESS CLASS II...EOSINOPHILS PRESENT ANTIGEN IN...AIRWAY EOSINOPHILS PRESENT...ANTIGEN PRESENTATION OF...REFERENCES |
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and IL-2, which initiate the killing of viruses and other intracellular organisms by activating macrophages and cytotoxic T cells [68
]. These two subgroups of Th cells arise in response to different immunogenic stimuli and cytokines, and they constitute an immunoregulatory loop: Cytokines from Th1 cells inhibit Th2 cells and vice versa. An imbalance in this reciprocal arrangement may be the key to asthma [69
].
As eosinophils can express the molecules associated with antigen presentation, stimulate CD4+ T cell proliferation, and localize to T cell-rich regions of draining lymph nodes [42
, 70
], it is necessary to explore the effects of antigen presentation of eosinophils on Th1/Th2 balance. MacKenzie and colleagues [70
] have established that purified eosinophils from IL-5-transgenic mice were able to induce IL-4, IL-5, and IL-13 production in Th2 cells in an antigen-specific manner. These cells did not produce IFN- on stimulation. Thus, eosinophils are able to induce proinflammatory cytokine secretion from CD4+ Th2 cells polarized in vitro. In a more recent study [71
], we extended the above findings and showed that eosinophils isolated and purified from the airways of mice challenged with aerosolized ovalbumin were capable of stimulating Th2 cytokine production indicative of Th2 cell expansion by presenting antigen in an in vitro assay. These results were consistent with the previous findings reported by Mackenzie and colleagues [70
]. In addition, we also showed that the expansion of Th2 cells caused by airway eosinophils was CD80- and CD86-dependent, as the production of IL-4, IL-5, and IL-13 could be inhibited by the blockade of the B7/CD28/CTLA-4 costimulatory pathway by using anti-CD80 or/and -CD86 mAb. In that study [71
], eosinophils from ovalbumin-sensitized and -challenged mice were instilled into tracheas of ovalbumin-sensitized mice, and draining paratracheal lymph nodes were taken 3 days thereafter and tested for cytokine production. We noted that like the in vitro experiments, lymph node cells yielded mainly cytokine production of IL-4, IL-5, and IL-13 but not of IFN-. The addition of exogenous antigen to these lymph node cells yielded even greater Th2 cytokine production, indicative that Th2 cells were primed in vivo by antigen presentation of eosinophils and ready for cytokine production. As expected, the endotracheal instillation of fixed, nonviable eosinophils induced no significant productions of Th2 cytokines. Thus, eosinophils have the potential to activate Th2 cells to release disease-modulating cytokines. These investigations highlight the potential of eosinophils to not only act as terminal effector cells but also to actively amplify allergic responses by promoting Th2 cell immunity.
In comparison with other cell types that are APCs, several properties of eosinophils likely combine to endow them with distinct roles as APCs. The first property would be their tissue localization. The normal localization of eosinophils within mucosal tissues of the respiratory and gastrointestinal tracts [72 ] would position them to encounter foreign antigens at these mucosal surfaces. Moreover, in allergic airway diseases, eosinophils are characteristically found directly within the lumen and secretions of airways [58 , 59 ] and could interact directly with inhaled allergens within the airways. Second, eosinophils have the capacity to transmigrate from the luminal surface of the mucosa into regional lymph nodes. Alveolar macrophages [73 ] and DCs [74 , 75 ] can also migrate from the airways into tissues, but in vivo antigen-pulsed macrophages do not transfer processed peptides to DCs [76 ], and alveolar macrophages do not function as APCs in vivo [77 , 78 ]. Finally, the expression of several Ig receptors on eosinophils might enable Ig-facilitated enhancement of antigen uptake and presentation by eosinophils, as shown for other APCs [79 80 81 ]. Human eosinophils express receptors for IgG, IgE, and IgA. In mucosal sites, eosinophils will be exposed to antibodies of all three classes, including IgG, IgE, and IgA antibodies to inhaled allergens [82 ].
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ACKNOWLEDGEMENTS |
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Received April 8, 2004; revised May 11, 2004; accepted May 13, 2004.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONEOSINOPHILS EXPRESS CLASS II...EOSINOPHILS PRESENT ANTIGEN IN...AIRWAY EOSINOPHILS PRESENT...ANTIGEN PRESENTATION OF...REFERENCES |
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regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells J. Exp. Med. 177,573-576 expression J. Immunol. 150,2554-2562[Abstract]
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RI) mediates IgE-dependent allergen presentation J. Immunol. 154,6285-6290[Abstract]
receptor (monocyte/macrophage)-specific immunogens J. Immunol. 149,3477-3481[Abstract]
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