Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Th2”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed1998

Characterization of cis-regulatory elements and nuclear factors conferring Th2-specific expression of the IL-5 gene: a role for a GATA-binding protein.

Expression of the IL-5 gene is restricted to the Th2 subset of helper T cells. We have previously defined four cis-regulatory elements of the IL-5 promoter responding to PMA and cAMP in EL-4 cells. We now report that the 1.2-kb region of the IL-5 promoter directs expression of the IL-5 gene in a Th2 clone but not a Th1 clone, indicating that transcription from the IL-5 promoter is Th2 specific. For the functioning of the IL-5 promoter in a Th2 clone, IL-5C and IL-5CLE0 were critical. IL-5CLE0 interacted with both constitutive and inducible nuclear factors (designated NFIL-5CLE0), which existed in both Th1 and Th2 clones, whereas IL-5C interacted with a constitutive nuclear factor (designated NFIL-5C), which was found only in Th2 but not in Th1 clones. Th2 specificity of NFIL-5C was also confirmed using in vitro-differentiated Th1 and Th2 cells derived from TCR-transgenic mice. The sequence for NFIL-5C binding bears homology with GATA-binding sites. The NFIL-5C complex was supershifted by an anti-GATA-3 Ab and inhibited by an oligonucleotide containing GATA-binding sites. We showed preferential expression of GATA-3 in Th2 cells. Finally, we demonstrated that in vitro-translated GATA-3 bound to IL-5C and overexpression of GATA-3 augmented stimulation-dependent IL-5 promoter activity in EL-4 cells. Taken together, our results provide evidence that GATA-related factors may be involved in Th2-specific expression of the IL-5 gene.

Animals↗
PubMed1989

Murine hepatic accessory cells support the proliferation of Th1 but not Th2 helper T lymphocyte clones.

The liver is the major site of clearance and degradation of foreign antigens from the portal circulation. Despite the presence of hepatic accessory cells, antibody responses to orally administered antigens are uncommon. To ascertain if hepatic accessory cells are incapable of stimulating specific subsets of T lymphocytes, freshly isolated hepatic nonparenchymal and splenic cells were cultured with a panel of antigen-specific, H-2-restricted Th1 and Th2 HTL clones. Whereas spleen cells stimulated the proliferation of both Th1 and Th2 clones, hepatic nonparenchymal cells (NPC) stimulated the proliferation of only Th1 and not Th2 clones. Adding rIL-1, rIL-6, and rIL-7, alone or in combination, to the cultures did not result in proliferation of the Th2 clones. Despite the absence of Th2 proliferation, NPC were able to stimulate the secretion of IL-3 and IL-4 by Th2 clones in the presence of antigen. Moreover, adding hepatic NPC did not inhibit spleen cells from stimulating Th2 clones in the presence of antigen. Thus, the inability of liver cells to stimulate the proliferation of Th2 helper T lymphocytes appears to be secondary to an absence of either an unknown accessory cell cofactor or an accessory cell that preferentially presents antigen to Th2 cells. The selective activation of Th1 and not Th2 cells by liver accessory cells may result in suppression of antibody responses to orally administered antigens.

Animals↗
PubMed1989

Antigen-specific activation of effector macrophages by IFN-gamma producing (TH1) T cell clones. Failure of IL-4-producing (TH2) T cell clones to activate effector function in macrophages.

IFN-gamma-producing (TH1) and IL-4-producing (TH2) clones were assayed for their ability to directly induce cytostatic activity in macrophages generated from splenic myeloid precursors (M phi-c). In the presence, but not in the absence, of antigen, TH1 clones activated the M phi-c to inhibit the growth of P815 tumor cells in vitro. TH2 clones were not able to activate such effector activity in the M phi-c. The M phi-c did effectively present Ag to the TH2 clones as evidenced by the proliferation of TH2 cells cultured with Ag in the presence, but not in the absence, of M phi-c. Therefore, although both TH1 and TH2 were activated by cognate interaction with antigen presenting M phi-c, only TH1:M phi-c interactions displayed reciprocity resulting in activation of the M phi-c. TH1-derived lymphokines or rIFN-gamma, in the presence of LPS, could activate proteose-peptone elicited M phi, resident peritoneal M phi, and M phi-c whereas neither TH2-derived lymphokines nor rIL4 could induce detectable activity in any of the 3 M phi populations. IFN-gamma, in the absence of LPS, could activate the elicited M phi and to a lesser and more variable degree, the resident M phi Only the M phi-c consistently required both IFN-gamma and LPS for induction of cytostatic activity. Since M phi-c consistently required at least two signals for activation, the ability of TH1-derived lymphokines to synergize with TH2 cells in M phi activation was examined. TH2 could activate the Ag-presenting M phi-c in the presence of IFN-gamma. The ability of added IFN-gamma to synergize with TH2 indicates that the cognate interaction between TH2 and antigen presenting M phi-c does result in delivery of at least one of the signal required for M phi activation.

Animals↗
PubMed1993

Human IL-10 is produced by both type 1 helper (Th1) and type 2 helper (Th2) T cell clones and inhibits their antigen-specific proliferation and cytokine production.

IL-10 gene transcription and IL-10 protein production was assessed in both type 1 (Th1) and type 2 (Th2) CD4+ human T cell clones by polymerase chain reaction and ELISA, respectively. Although Th2 clones apparently showed higher IL-10 mRNA levels, IL-10 mRNA expression was consistently found in Th1 clones, as well. Likewise, measurable IL-10 levels were found in the supernatants of both Th1 and Th2 clones. The effect of human IL-10 (h-IL-10) and viral IL-10 (v-IL-10) on the proliferative response and cytokine production by Th1 and Th2 human clones was also investigated. Addition in culture of h-IL-10 and v-IL-10 significantly reduced the proliferation of both Th1 and Th2 clones in response to the specific Ag and to PHA, but it had no inhibitory effect on the proliferative response of Th1 and Th2 clones to IL-2. h-IL-10 and v-IL-10 also inhibited the Ag-induced production of gamma-interferon (IFN-gamma) by Th1 clones and the production of IL-4 and IL-5 by Th2 clones, whereas they had no effect on the cytokine synthesis by the same clones stimulated with PMA plus anti-CD3 antibody. Preincubation of APC, but not of clonal T blasts, with h-IL-10 resulted in the inhibition of Ag-induced proliferation of both Th1 and Th2 clones, supporting the view that h-IL-10 primarily affects APC. These data demonstrate that, unlike the murine system where IL-10 is a product of Th2 (but not Th1) cells and seems to mainly down-regulate the Th1 response, in the human system, IL-10 is produced by, and down-regulates the function of, both Th1 and Th2 cells.

Animals↗
PubMed1993

T cell-macrophage cognate interaction in the activation of macrophage effector function by Th2 cells.

The in vitro induction of cytostatic/cytotoxic activity in macrophages generated in spleen cell cultures requires a signal cascade initiated by costimulation with both LPS and IFN-gamma. Th2 lymphocytes, although they do not produce IFN-gamma, can provide the signals necessary for induction of cytostatic activity in IFN-gamma-primed macrophages. These signals appear to be delivered by cognate interaction between the Th2 cells and macrophages in that: 1) they are not delivered by culture supernatants of Th2 cells activated 6 or 20 h by Con A or by immobilized anti-CD3 mAb; 2) they are not delivered if cell contact between Th2 cells and macrophages is prevented; and 3) they can be delivered by paraformaldehyde-fixed activated Th2 cells. Paraformaldehyde-fixed resting Th2 cells cannot stimulate activation of INF-gamma-primed macrophages. The Th2 cells must be activated at least 3 h before fixation to acquire macrophage stimulatory activity. Optimal macrophage-stimulating activity is attained after 6-h activation of the Th2 and declines thereafter. Although the activation of IFN-gamma-primed macrophages by viable resting Th2 displays Ag specificity and MHC restriction, the activation of IFN-gamma-primed macrophages by paraformaldehyde-fixed activated Th2 is neither Ag specific nor MHC restricted. These observations suggest that T cell-mediated activation of macrophages can involve a signaling cascade of Ag-specific and Ag-nonspecific adhesion events comparable to those hypothesized to occur in T cell-mediated B cell activation.

Animals↗
PubMed1998

Th1 cells induce and Th2 inhibit antigen-dependent IL-12 secretion by dendritic cells.

Dendritic cells are the most relevant antigen-presenting cells (APC) for presentation of antigens administered in adjuvant to CD4+ T cells. Upon interaction with antigen-specific T cells, dendritic cells (DC) expressing appropriate peptide-MHC class II complexes secrete IL-12, a cytokine that drives Th1 cell development. To analyze the T cell-mediated regulation of IL-12 secretion by DC, we have examined their capacity to secrete IL-12 in response to stimulation by antigen-specific Th1 and Th2 DO11.10 TCR-transgenic cells. These cells do not differ either in TCR clonotype or CD40 ligand (CD40L) expression. Interaction with antigen-specific Th1, but not Th2 cells, induces IL-12 p40 and p75 secretion by DC. The induction of IL-12 production by Th1 cells does not depend on their IFN-gamma secretion, but requires direct cell-cell contact mediated by peptide/MHC class II-TCR and CD40-CD40L interactions. Th2 cells not only fail to induce IL-12 secretion, but they inhibit its induction by Th1 cells. Unlike stimulation by Th1, inhibition of IL-12 production by Th2 cells is mediated by soluble molecules, as demonstrated by transwell cultures. Among Th2-derived cytokines, IL-10, but not IL-4 inhibit Th1-driven IL-12 secretion. IL-10 produced by Th2 cells appears to be solely responsible for the inhibition of Th1 -induced IL-12 secretion, but it does not account for the failure of Th2 cells to induce IL-12 production by DC. Collectively, these results demonstrate that Th1 cells up-regulate IL-12 production by DC via IFN-gamma-independent cognate interaction, whereas this is inhibited by Th2-derived IL-10. The inhibition of Th1 -induced IL-12 production by Th2 cells with the same antigen specificity represents a novel mechanism driving the polarization of CD4+ T cell responses.

Animals↗
PubMed2003

Predominant expression of the Th2 response in chronic cardiac allograft rejection.

Chronic rejection is the main cause of late allograft failure in patients. CD4+ T cells activated by indirect recognition of alloantigens are implicated in this rejection reaction. However, the type of T cell response (Th1 vs Th2) that contributes to chronic rejection has not been fully investigated. The purpose of this study is to examine whether chronic rejection is associated with a polarized T-cell response in a rat cardiac allograft model, where long-term graft survival is achieved by intrathymic immunomodulation with donor class I, RT1.Aa, allopeptides. All long-surviving allografts showed histological evidence of chronic rejection. Chronic rejection was associated with high levels of intragraft Th2 cytokines and the Th2-regulated alloantibodies. The Th2 response was systemic, since long-surviving allografts with chronic rejection had high levels of serum IL-10. The predominance of the Th2 cytokines demonstrates that the Th2 response was not sufficient for the prevention of chronic rejection in this model. The predominant expression of Th2 cytokines, together with the presence of Th2-regulated alloantibodies, suggests that the Th2 response may play a role in the development of chronic rejection.

Adjuvants, Immunologic↗
PubMed2003

Replication at the level of reverse transcription of HIV-1SF2 strain in Th1 and Th2 cells.

It has been reported that Th2 cells better support replication of T-tropic HIV-1 strain than Th1 cells. We investigated at the level of reverse transcription the replication of T-tropic HIV-1SF2 strain in Th1 and Th2 cells. To determine the presence of the early (RU5), intermediate (gag) and full-length (LTR/gag) product of reverse transcription of virus RNA in Th1 and Th2 cells, we employed the PCR technique. Our results revealed that the early (RU5) product of reverse transcription was detectable 30 min after infection in Th2 cells and 1 h after infection in Th1 cells. The product of reverse transcription corresponding to the gag region of HIV-1 was detected in Th2 cells 2 h after infection, whereas the same fragment of viral DNA in Th1 cells was observed 4 h later. The full-length viral DNA was seen in Th2 cells 6 h after infection but the same time course was not detected in the Th1 cells. We also observed that higher efficiency of reverse transcription of viral RNA correlated with better replication of HIV-1SF2 in Th2 than Th1 cells. The higher concentration of p24 HIV-1 antigen in culture medium than cytoplasm of Th1 and Th2 cells confirmed the lack of restriction at the budding step of HIV-1SF2 replication in Th1 and Th2 cells. Our observation may confirm the suggestion that Th0/Th2 cell orientation supports at the reverse transcriptional level the replication of T-tropic HIV-1 strains, which accelerates the onset of AIDS symptoms.

Adult↗
PubMed2000

Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment.

The initial source of IL-4-inducing Th2 development and the mechanism of stable Th2 commitment remain obscure. We found the reduced level of IL-4 production in Stat6-deficient T cells to be significantly higher than in Th1 controls. Using a novel cell surface affinity matrix technique, we found that IL-4-secreting Stat6-deficient T cells stably expressed GATA-3 and Th2 phenotype. Introducing GATA-3 into Stat6-deficient T cells completely restored Th2 development, inducing c-Maf, Th2-specific DNase I hypersensitive sites in the IL-4 locus, and Th2 cytokine expression. The fact that GATA-3 fully reconstitutes Th2 development in Stat6-deficient T cells indicates it is a master switch in Th2 development. Finally, GATA-3 exerts Stat6-independent autoactivation, creating a feedback pathway stabilizing Th2 commitment.

Animals↗
PubMed2007

3D computation modelling of the influence of cytokine secretion on Th-cell development suggests that negative selection (inhibition of Th1 cells) is more effective than positive selection by IL-4 for Th2 cell dominance.

Th-cell development has been suggested to include selective mechanisms in which certain cytokines select either Th1 or Th2 cells to proliferate and grow. The selective theory is based on the observation that Th2 cells secrete IL-4, a cytokine that promotes Th2 development, whereas Th1 cells secrete interferon-gamma (IFN-gamma) that favours Th1 development, and both positive and negative selective influences have been suggested to operate. In this study, we investigate the role of autocrine secretion and utilization of IL-4 by Th2 cells and address the question of whether an activated Th2 cell can be positively selected by IL-4 secreted from other Th2 cells. We present a spatial three dimensional (3D) modelling approach to simulate the interaction between the IL-4 ligand and its IL-4 receptors expressed on discrete IL-4 secreting cells. The simulations, based on existing experimental data on the IL-4 receptor-ligand system, illustrate how Th-cell development is highly dependent on the distance between cells that are communicating. The model suggests that a single Th2 cell is likely to communicate with possible target cells within a range of approximately 100 microm and that an activated Th2 cell manages to fill most of its own IL-4 receptors, even at a low secretion rate. The predictions made by the model suggest that negative selection against Th1 cells is more effective than positive selection by IL-4 for promoting Th2 dominance.

Animals↗
PubMed2002

Regulatory functions of alloreactive Th2 clones in human renal transplant recipients.

BACKGROUND: Chronic allograft rejection is the major clinical problem in organ transplantation. There is evidence that indirect T cell recognition of donor-specific HLA peptides may play an important role in the immunopathogenesis of chronic allograft rejection. We have recently shown that HLA allopeptide-specific T cell clones generated from renal transplant recipients with chronic allograft nephropathy are of the Th1 phenotype, while those from stable patients are Th2. There is evidence in experimental animal models of autoimmunity and transplantation that Th2 cells may function to regulate immune responses, but the biological relevance of these observations in humans has not been reported. METHODS: The purpose of this study was to investigate the putative regulatory functions of alloreactive human Th2 clones. HLA-DR allopeptide-specific Th1 and Th2 cell clones were generated from peripheral blood lymphocytes of human renal allograft recipients with chronic allograft nephropathy (CAN) or with stable renal function (SRF), respectively. RESULTS: An in vitro co-culture system showed that the proliferative responses of Th1 clones from patients with CAN were significantly inhibited by the Th2 clones in response to the donor-derived HLA allopeptides. In addition, co-culture of the Th2 clones inhibited cytokine production (IFN-gamma) by the Th1 clones in response to the donor-specific peptides. The regulatory functions of Th2 clones were antigen-specific since they only occurred when both the Th1 and Th2 clones were reactive to the same HLA-DR allopeptide, and were mediated by IL-4 and IL-10. CONCLUSIONS: This is the first demonstration, to our knowledge, indicating that Th2 cells may function to regulate indirect Th1 alloimmune responses that are critical for the progression of CAN in humans.

Antibodies, Monoclonal↗
PubMed1997

Induction of airway mucus production By T helper 2 (Th2) cells: a critical role for interleukin 4 in cell recruitment but not mucus production.

Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4-deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-alpha, IL-4 -/- Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

Adoptive Transfer↗
PubMed1997

Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease.

Chronic inflammatory autoimmune diseases such as multiple sclerosis, diabetes, and rheumatoid arthritis are caused by CD4(+) Th1 cells. Because Th2 cells antagonize Th1 cell functions in several ways, it is believed that immune deviation towards Th2 can prevent or cure autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease used as a model for multiple sclerosis. Using an adoptive transfer system we assessed the role of Th1 and Th2 cells in EAE. In vitro generated Th1 and Th2 cells from myelin basic protein (MBP)-specific TCR transgenic mice were transferred into normal and immunodeficient mice. Th1 cells caused EAE in all recipients after a brief preclinical phase. Surprisingly, Th2 cells also caused EAE in RAG-1 KO mice and in alphabeta T cell-deficient mice, albeit after a longer preclinical phase. Normal or gammadelta T cell-deficient mice were resistant to EAE induced by Th2 cells. The histopathological features of this disease resembled those of an allergic process. In addition, disease induction by Th1 cells was not altered by coadmininstration of Th2 cells in any of the recipients. These findings indicate that MBP-specific Th2 cells have the potential to induce EAE and that the disease induced by previously activated Th1 cells cannot be prevented by normal lymphocytes nor by previously activated Th2 cells.

Animals↗
PubMed2005

Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction.

A single treatment with a CpG-containing immunostimulatory DNA sequence (ISS) given before allergen challenge can inhibit T helper type 2 cell (Th2)-mediated airway responses in animal models of allergic asthma; however, the mechanism of this inhibition remains largely undefined. Here, we demonstrate that airway delivery of ISS before allergen challenge in Th2-primed mice acts in two distinct ways to prevent the allergic responses to this challenge. The first is to prevent induction of cytokines from allergen-specific Th2 cells, as demonstrated by the nearly complete inhibition of Th2 cytokine production, Th2-dependent functional responses, and gene induction patterns. ISS inhibits the Th2 response by rendering lung antigen-presenting cells (APCs) unable to effectively present antigen to Th2 cells, but not to Th1 cells. This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c(+ )APCs from the airways of ISS-treated mice. The second important action of ISS is inhibition of immunoglobulin E-dependent release of Th2 cytokines, especially interleukin 4, from basophils and/or mast cells in the airways of Th2-primed mice. Thus, inhibition by ISS of allergic responses can be explained by two novel mechanisms that culminate in the inhibition of the principal sources of type 2 cytokines in the airways.

Adjuvants, Immunologic↗
PubMed2004

VIP/PACAP preferentially attract Th2 effectors through differential regulation of chemokine production by dendritic cells.

The neuropeptides vasoactive intestinal peptide (VIP) and the structurally related pituitary adenylate cyclase-activating polypeptide (PACAP) are potent immunomodulatory agents, acting as general anti-inflammatory factors. VIP, produced and secreted by Th2 cells following antigen stimulation, participates in a Th2 autoregulatory loop, promoting Th2-type responses through several nonexcluding mechanisms. VIP and PACAP affect the differentiation of CD4+ T cells directly and indirectly through antigen-presenting cells and promote the proliferation and/or survival of the Th2 effectors. Th1 and Th2 effectors express different chemokine receptors that control migration in response to various chemokines. In this study, we investigated the effects of VIP/PACAP on the production of CXCL10 (a Th1 chemokine) and of CCL22 (a Th2 chemokine) by bone marrow-derived dendritic cells. We found that VIP and PACAP inhibit CXCL10, while promoting CCL22 production, and that the effects are mediated through the VPAC1 receptor and involve cAMP/PKA as intracellular messengers. The induction of CCL22 and the suppression of CXCL10 in VIP/PACAP-treated dendritic cells results in the preferential chemoattraction of Th2 effectors both in vivo and in vitro. This is in agreement with the general Th2 bias induced by the two neuropeptides and adds an important parameter to their immunomodulatory function. By promoting Th2 migration, and preventing or reducing Th1 infiltration in inflammatory foci and sites of antigen presentation, VIP and PACAP help in resolving acute inflammatory processes and contribute to the prevention of chronic inflammation.

Animals↗
PubMed2004

Effect of IL-12 and soluble IL-4 receptor on the herpesvirus infection in human SCID chimeras whose Th2 cells predominate.

Th2 cytokines, commonly detected in burn patients, have been shown as inhibitors for the generation of Th1 cells that are essential for the host's resistance against herpes simplex virus type 1 (HSV-1) infection. In this study, the possibility of immunological treatment through the regulation of Th1/Th2 responses was examined in two kinds of human severe combined immunodeficiency (SCID) chimera models reflecting human immune functions. SCID mice injected with a mixture of PBMC from a healthy donor and Th2 cells experimentally generated from the same healthy PBMC (Th2 SCID chimeras) were more susceptible to HSV-1 infection when compared with SCID mice injected with healthy donor PBMC (healthy SCID chimeras). When Th2 SCID chimeras were individually treated with human IL-12 (hIL-12) or human soluble IL-4 receptor (hsIL-4R), hIFN-gamma was not produced in their sera after antihuman CD3 mAb stimulation. However, hIFN-gamma production in sera of Th2 SCID chimeras treated with the combination therapy of hIL-12 and hsIL-4R was recovered at levels observed in healthy SCID chimeras. When Th2 SCID chimeras infected with HSV-1 were treated with saline, hIL-12, hsIL-4R or a combination of hIL-12 and hsIL-4R, 13%, 13%, 25% or 100% of them survived, respectively. Also, Th1 responses (hIFN-gamma production) were demonstrated in Th2 SCID chimeras that became resistant against HSV-1 infection after the combination treatment. These results suggest that individuals whose Th2 cells predominated may be immunologically controlled by the combination treatment between a Th1 response inducer and a Th2 response inhibitor.

Animals↗
PubMed2005

Differential expression of inflammatory chemokines by Th1- and Th2-cell promoting dendritic cells: a role for different mature dendritic cell populations in attracting appropriate effector cells to peripheral sites of inflammation.

Protective immunity to pathogens depends on efficient immune responses adapted to the type of pathogen and the infected tissue. Dendritic cells (DC) play a pivotal role in directing the effector T cell response to either a protective T helper type 1 (Th1) or type 2 (Th2) phenotype. Human monocyte-derived DC can be differentiated into Th1-, Th2- or Th1/Th2-promoting DC in vitro upon activation with microbial compounds or cytokines. Host defence is highly dependent on mobile leucocytes and cell trafficking is largely mediated by the interactions of chemokines with their specific receptors expressed on the surface of leucocytes. The production of chemokines by mature effector DC remains elusive. Here we assess the differential production of both inflammatory and homeostatic chemokines by monocyte-derived mature Th1/Th2-, Th1- or Th2-promoting DC and its regulation in response to CD40 ligation, thereby mimicking local engagement with activated T cells. We show that mature Th1- and Th1/Th2-, but not Th2-promoting DC, selectively express elevated levels of the inflammatory chemokines CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL5/RANTES, as well as the homeostatic chemokine CCL19/MIP-3beta. CCL21/6Ckine is preferentially expressed by Th2-promoting DC. Production of the Th1-attracting chemokines, CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC, is restricted to Th1-promoting DC. In contrast, expression of Th2-associated chemokines does not strictly correlate with the Th2-promoting DC phenotype, except for CCL22/MDC, which is preferentially expressed by Th2-promoting DC. Because inflammatory chemokines and Th1-associated chemokines are constitutively expressed by mature Th1-promoting DC and CCL22/MDC is constitutively expressed by mature Th2-promoting DC, we propose a novel role for mature DC present in inflamed peripheral tissues in orchestrating the immune response by recruiting appropriate leucocyte populations to the site of pathogen entry.

Cell Movement↗
PubMed2007

Differential expression of neutrophilic granule proteins between Th1 and Th2 cells.

T helper cell type 1 (Th1) and 2 (Th2) play central roles in immune regulation. To identify the novel genes differentially expressed between Th1 and Th2 cells, CD4+ T cells were isolated from DO11.10 transgenic mice and induced under Th1 or Th2 conditions. Microarray showed differential expression of neutrophilic granule proteins (NGP) between Th1 and Th2 cells. NGP was first identified as a myeloid-specific granule protein with homology to the cystatin superfamily. Here we confirmed greater expression of NGP in Th2 cells by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction analysis. We also showed that the expression of NGP mRNA had a peak expression after 5 d culture under Th2- but not Th1-biasing conditions. Antibody against NGP was prepared, and in concert with the results of mRNA analysis, the level of NGP protein in Th2 cells detected by Western blot analysis was also higher than that in Th1 cells. GFP-NGP fusion proteins overexpressed in HeLa cells were localized to the cytoplasm. These results suggest NGP is a novel marker distinguishing Th2 from Th1 cells and maybe a novel cytokine secreted by Th2 cells.

Animals↗