Requirement of CD80 and CD86 Molecules for Antigen Presentation by Eosinophils

293

218

In this investigation, we have examined the integrated relationship between IL-13, IL-4, and IL-5 for the development of airways hyperreactivity (AHR) in a model of asthma in BALB/c mice. Sensitization and aeroallergen challenge of both wild-type (WT) and IL-13 gene-targeted (IL-13−/−) mice induced allergic disease that was characterized by pulmonary eosinophilia and AHR to β-methacholine. Although these responses in IL-13−/− mice were heightened compared with WT, they could be reduced to the level in nonallergic mice by the concomitant neutralization of IL-4. Mice in which both IL-4 and IL-13 were depleted displayed a marked reduction in tissue eosinophils, despite the development of a blood eosinophilia. Similar neutralization of IL-4 in WT mice only partially reduced AHR with no effect on tissue eosinophilia. In addition, neutralization of IL-5 in IL-13−/− mice, but not in WT mice, inhibited AHR, suggesting that tissue eosinophilia is linked to the mechanism underlying AHR only in the absence of IL-13. Additionally, mucus hypersecretion was attenuated in IL-13−/− mice, despite the persistence of AHR. Taken together, our data suggest both a modulatory role for IL-13 during sensitization and a proinflammatory role during aeroallergen challenge. The latter process appears redundant with respect to IL-4.

Section: Discussionmentioning

confidence: 99%

Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity

Webb

McKenzie

Koskinen

et al. 2000

293

218

“…An explanation for this phenomenon could be that cytokines secreted by allergic lung cells could up-regulate MHCII expression on eosinophils. Several cytokines like IFN-␥, IL-3, and GM-CSF secreted by inflammatory cells are reported to induce MHCII expression in vitro (5,17,19). In support of this, eosinophils from the peritoneal cavity of IL-5 Tg mice that were purified using Percoll gradients and adherence steps were reported to have no MHCII expression, except when cultured with GM-CSF (19).…”

Section: Figure 4 Sorting Eosinophils From Balf Cells Were Sorted Amentioning

confidence: 95%

“…Several cytokines like IFN-␥, IL-3, and GM-CSF secreted by inflammatory cells are reported to induce MHCII expression in vitro (5,17,19). In support of this, eosinophils from the peritoneal cavity of IL-5 Tg mice that were purified using Percoll gradients and adherence steps were reported to have no MHCII expression, except when cultured with GM-CSF (19). Others showed that BALF eosinophils isolated using Percoll gradients and adherence culture weakly expressed MHCII, probably because of GM-CSF release in vivo (7).…”

Section: Figure 4 Sorting Eosinophils From Balf Cells Were Sorted Amentioning

confidence: 99%

Airway Eosinophils Accumulate in the Mediastinal Lymph Nodes but Lack Antigen-Presenting Potential for Naive T Cells

Rijt

Vos

Hijdra

et al. 2003

Asthma is characterized by infiltration of the airway wall with eosinophils. Although eosinophils are considered to be effector cells, recent studies have reported their ability to activate primed Th2 cells. In this study, we investigated whether eosinophils are capable of presenting Ag to unprimed T cells in draining lymph nodes (DLN) of the lung and compared this capacity with professional dendritic cells (DC). During development of eosinophilic airway inflammation in OVA-sensitized and challenged mice, CCR3+ eosinophils accumulated in the DLN. 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 intratracheally injected into mice that previously received CFSE-labeled OVA TCR-transgenic T cells. Eosinophils did not induce divisions of T cells in the DLN, whereas DC induced on average 3.7 divisions in 45.7% of T cells. To circumvent the need for Ag processing or migration in vivo, eosinophils were pulsed with OVA peptide and were still not able to induce T cell priming in vitro, whereas DC induced vigorous proliferation. This lack of Ag-presenting ability was explained by the very weak expression of MHC class II on fresh eosinophils, despite expression of the costimulatory molecules CD80 and ICAM-1. This investigation does not support any role for airway eosinophils as APCs to naive T cells, despite their migration to the DLN at times of allergen exposure. DC are clearly superior in activating T cells in the DLN of the lung.

“…Conventionally associated with host defense against parasitic infection, through degranulation and release of toxic proteins, eosinophils also produce a variety of pro-and anti-inflammatory cytokines, growth factors, and chemokines (10 -13). Eosinophils can act as APC (14,15) and express several important costimulatory molecules (11,16), indicating that they could modulate adaptive immune responses. Eosinophils marginated in respiratory, gut, and urogenital subepithelium represent 95% of the total population, yet their physiological role is unclear.…”

mentioning

confidence: 99%

CD11c+ Eosinophils in the Murine Thymus: Developmental Regulation and Recruitment upon MHC Class I-Restricted Thymocyte Deletion

Throsby

Herbelin

Pleau

et al. 2000

110

100

Eosinophils are bone marrow-derived cells released into the circulation during hypersensitivity reactions and parasitic infections. Under normal conditions most eosinophils are tissue bound, where their physiologic role is unclear. During in situ analysis of the thymic microenvironment for CD11c+ dendritic cell subpopulations (APC critical in the process of thymic negative selection) a discrete population of CD11b/CD11c double-positive cells concentrated in the cortico-medullary region of young mice was detected. Thymic CD11c+ cells were isolated, and the CD11b+ subpopulation (CD44high, class IIlow, CD11cint) was identified as mature eosinophils based on: scatter characteristics, major basic protein mRNA expression, and eosinophilic granules. They are hypodense, release high levels of superoxide anion, and express CD25, CD69, and mRNA for IL-4 and IL-13, but not GM-CSF or IL-5, suggesting a distinct state of activation. Thymic eosinophils are preferentially recruited during the neonatal period; absolute numbers increased 10-fold between 7–14 days to reach parity with dendritic cells before diminishing. In a model of acute negative selection, eosinophil numbers were increased 2-fold 6 h after cognate peptide injection into MHC class I-restricted female H-Y TCR transgenic mice. In both peptide-treated female and negatively selecting male H-Y TCR mice, clusters of apoptotic bodies were associated with eosinophils throughout the thymus. Our data demonstrate a temporal and spatial association between eosinophil recruitment and class I-restricted selection in the thymus, suggesting an immunomodulatory role for eosinophils under nonpathological conditions.