Expression of Chemokine Receptors by Lung T Cells from Normal and Asthmatic Subjects

Campbell, James J.; Brightling, Christopher E.; Symon, F A; Qin, S.; Murphy, Kristine; Hodge, Mmarty; Andrew, David P.; Wu, Lijun; Butcher, Eugene C.; Wardlaw, Andrew J.

doi:10.4049/jimmunol.166.4.2842

Cited by 161 publications

(135 citation statements)

References 29 publications

(24 reference statements)

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…However, in contrast to this, mice-deficient in the CCR4 gene did not show a significant difference in predisposition to the development of allergic lung inflammation compared with wild-type mice (24). Furthermore, studies examining the expression of chemokine receptors on T lymphocytes isolated from the BALF of asthmatic and non-asthmatic individuals showed that CCR4 expression on T lymphocytes at these sites was not significantly different between these groups (26). However, CCR4 has been shown to be significantly up-regulated within the lung tissue of asthmatics following allergen challenge (27).…”

Section: Discussionmentioning

confidence: 86%

“…In contrast to this, CCR4-deficient mice showed no significant difference in predisposition to allergic lung inflammation compared with wild-type mice (24) perhaps supporting the existence of an additional MDC receptor as other researchers have proposed (25). In humans, examination of chemokine receptor expression on T lymphocytes isolated from the bronchoalveolar fluid (BALF) of asthmatics or non-asthmatic individuals indicated that CCR4 is expressed at similar levels (5%) in each of these groups (26). However, Panina-Bordignon et al (27) demonstrated that, following allergen challenge of asthmatics, significant up-regulation of CCR4, and to a lesser extent CCR8, was observed in the lung tissue, with a corresponding upregulation of MDC and TARC expressed on the airway epithelium.…”

Section: However Ccr4mentioning

confidence: 99%

See 1 more Smart Citation

The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody

Jopling¹,

Sabroe²,

Andrew³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Th2 lymphocytes play a central role in the control and maintenance of allergic inflammation. The chemokine receptor CCR4 is preferentially expressed on the surface of Th2 lymphocytes polarised in vitro. However, CCR4 is found on the surface of a significant proportion of circulating memory T lymphocytes, some of which are capable of producing the Th1-associated cytokine interferon ␥. To investigate the function of CCR4 on guinea pig (gp) T lymphocytes, we identified the open-reading frame of gpCCR4, which encodes a 361-amino acid protein with 88 and 81% amino acid identity to human and murine CCR4 sequences, respectively. Cells transfected with gpCCR4 migrated toward the human and murine orthologues of the CCR4 ligands, macrophage-derived chemokine and thymus and activation-regulated chemokine. Surface expression of CCR4, using an anti-human CCR4 monoclonal antibody, 10E4, was detected on ϳ12% of guinea pig peripheral blood T helper cells, and CCR4 ؉ guinea pig thymocytes were detected in low numbers. However, CCR4؉ T helper cells constituted ϳ9% of the T lymphocyte population within the normal guinea pig lung and 52% of the guinea pig bronchoalveolar lavage fluid, which is consistent with a role for CCR4 in T lymphocyte development and trafficking through normal tissues. Subsequent analysis of chimeric chemokine receptors indicated that 10E4, a functional inhibitor of gpCCR4 responses, recognized the amino terminus of CCR4.Allergic inflammation of the lung in diseases such as asthma is largely controlled and maintained by the recruitment of antigen-specific T lymphocytes to the lung tissue (1). The Th2-type lymphocytes that predominate at sites of allergic inflammation secrete cytokines such as IL-4, IL-5 and IL-13, 1 which influence the actions of other leukocyte populations involved in the inflammatory response (2, 3). For example, IL-4 and IL-13 can induce B lymphocyte production of IgE (4, 5) and airway epithelial cell generation of eotaxin, which is central to eosinophil recruitment (6, 7), whereas IL-5 is a potent eosinophil maturation and survival factor (8, 9). Overexpression of IL-13 in the lung causes many of the histopathological and physiological features of asthma (10). Increasing evidence suggests that chemokines are important regulators of the selective trafficking of leukocytes in homeostasis, hematopoiesis, and inflammation (11). Chemokines can be divided into four subfamilies dependent upon the position of their amino-terminal cysteine residues; the two main chemokine groups are the CXCL and the CCL subfamilies (12), which signal via CXCR and CCR receptors belonging to the G-protein coupled receptor superfamily (13,14). The differential expression of chemokine receptors on the surface of leukocytes contributes to the selective recruitment of cells to specific sites, and, consequently, these receptors may provide useful targets for therapeutic intervention in the modulation of inflammatory disorders. Studies of T lymphocytes polarized in vitro have shown that Th1 cells preferentially express CC...

show abstract

Section: Discussionmentioning

confidence: 86%

Section: However Ccr4mentioning

confidence: 99%

The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody

Jopling¹,

Sabroe²,

Andrew³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…30,31,[63][64][65] Although considerable attention has given to T-cell expression of this chemokine receptor, more recent studies have elucidated CCR4 expression on a wide array of immune and nonimmune cells. 66,67 Using immunohistochemistry, we observed in the present study that resident alveolar macrophages in the naïve lung stained intensely for CCR4 but other resident cells including bronchial epithelium and smooth muscle were Figure 9.…”

Section: Discussionmentioning

confidence: 99%

“…28 Nonimmune cells such as those of epithelial, endothelial, or fibroblastic origin do not constitutively nor are they induced to express CCL22. 27 Both ligands bind CCR4, 28,29 a chemokine receptor shown to be expressed on various T-cell subsets including Th2 cells, 11,28,30,31 natural killer cells, 32 dendritic cells, and macrophages. 33 The pulmonary granulomatous response is a highly effective albeit potentially tissue-damaging response to the presence of poorly digestible elements in several organ systems including the lung.…”

mentioning

confidence: 99%

Role of CCR4 Ligands, CCL17 and CCL22, During Schistosoma mansoni Egg-Induced Pulmonary Granuloma Formation in Mice

Jakubzick

Wen

Matsukawa

et al. 2004

The American Journal of Pathology

View full text Add to dashboard Cite

Controversy persists pertaining to the role of CCR4 ligands, namely CCL17 (or thymus and activation regulated chemokine; TARC) and CCL22 (or macrophagederived chemokine; MDC), in Th2-type cytokine-dominated responses in the lung. Accordingly, the present study addressed the relative role of each of these CC chemokines during an evolving pulmonary granulomatous response elicited by the intrapulmonary embolization of live Schistosoma mansoni eggs into S. mansoni-sensitized mice. CCL22 protein expression peaked at day 4, but CCL17 levels were not increased significantly at any time after egg challenge. CCR4 transcript and protein expression were highest at day 8 after egg embolization and CCR4 protein was prominently expressed in macrophages surrounding S. mansoni eggs. Systemic immunoneutralization of CCL22 from the time of egg injection into S. mansonisensitized mice for 8 days significantly decreased CCR4 protein expression, the eosinophil content, the overall size of the egg granuloma, and its hydroxyproline content. Whole lung levels of interferon-␥ were also significantly increased at day 8 in anti-CCL22-treated mice. The systemic immunoneutralization of CCL17 had a lesser effect on all of the granuloma parameters listed above, but this antibody treatment significantly decreased granuloma hydroxyproline content to a greater extent than the anti-CCL22 antibody treatment. In addition, the immunoneutralization of CCL17 significantly increased whole lung levels of interleukin (IL)-4, IL-5, IL-13, transforming growth factor-␤, IL-12, and tumor necrosis factor-␣ at day 8 after egg infusion. Thus, these studies demonstrate a major role for CCL22 and a lesser role for CCL17 during an evolving S. mansoni egg granuloma in the lung. Understanding the biology of chemotactic cytokines or chemokines and their receptors continues to challenge a number of researchers working in diverse fields such as inflammation, immune regulation, angiogenesis, virology, and lymphoid development.

show abstract

“…Cell aliquots below this viability were discarded. Although no experiments were performed to test the effect of freezing conditions on both cytokine/chemokine production and cell surface CCR expression, previous studies showed that cryopreservation of cells from blood and bronchoalveolar lavages does not affect the pattern of expression of these molecules and that such cells possessed an ability in cytokine production and CCR expression as good as that of the fresh cells (34,35).…”

Section: Freezing Procedures and Cell Storagementioning

confidence: 99%

Mycobacterium tuberculosisAntigens Specifically Modulate CCR2 and MCP-1/CCL2 on Lymphoid Cells from Human Pulmonary Hilar Lymph Nodes

Arias

Jaramillo

López

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Macrophages and dendritic cells are involved in the immune response to Mycobacterium tuberculosis (Mtb). Such a response, although extensively studied using animal models and cells from human blood, has not been characterized in cells from pulmonary hilar lymph nodes (PHLN). We characterized populations of myeloid APC from PHLN and determined their expression of CCR2, CCR5, CCR7, CD40, CD54, CD80, and CD86 as well as the cytokine/chemokine microenvironment before and after purified protein derivative (PPD) and mannosilated lipoarabinomannan (ManLAM) stimulation. Results show that there are at least three APC populations in PHLN, defined as CD14highHLA-DRlow/−, CD14dimHLA-DRdim, and CD14−HLA-DRhigh/dendritic cells (DC), with the largest number represented by CD14dimHLA-DRdim cells (where dim indicates intermediate levels). CD14−HLA-DRhigh/DC expressed higher levels of costimulatory molecules and lower levels of CCR2 and CCR5, but all cell populations showed similar CCR7 levels. PPD and ManLAM specifically down-regulated CCR2 expression but not that of CCR5 and CCR7, and such down-regulation was observed on all APC populations. Mtb Ag did not affect the expression of costimulatory molecules. PPD but not ManLAM specifically induced MCP-1/CCL2 production, which was likely associated with the induction of IFN-γ because this cytokine was highly induced by PPD. We characterized, for the first time, different APC from human PHLN and show that Mtb Ag exert fine and specific regulation of molecules closely associated with the immune response to Mtb infection. Because knowledge of this response in secondary lymphoid tissues is still poorly understood in humans, such studies are necessary and important for a better understanding of lymphoid cell microenvironment and migrating capacities and their role in the immunopathogenesis of tuberculosis.

show abstract

Expression of Chemokine Receptors by Lung T Cells from Normal and Asthmatic Subjects

Cited by 161 publications

References 29 publications

The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody

The Identification, Characterization, and Distribution of Guinea Pig CCR4 and Epitope Mapping of a Blocking Antibody

Role of CCR4 Ligands, CCL17 and CCL22, During Schistosoma mansoni Egg-Induced Pulmonary Granuloma Formation in Mice

Mycobacterium tuberculosisAntigens Specifically Modulate CCR2 and MCP-1/CCL2 on Lymphoid Cells from Human Pulmonary Hilar Lymph Nodes

Contact Info

Product

Resources

About