scholarly journals The role of chorionic gonadotropin in the formation of immunological tolerance during pregnancy

2011 ◽  
Vol 57 (5) ◽  
pp. 52-56 ◽  
Author(s):  
S V Shirshev ◽  
S A Zamorina
Keyword(s):  
T Lymphocytes ◽  
Chorionic Gonadotropin ◽  
Mononuclear Cells ◽  
Active Oxygen Species ◽  
Relative Number ◽  
Immunological Tolerance ◽  
Interleukin 4 ◽  
Ifn Γ

We have studied the role of pregnancy hormone (chorionic gonadotropin, CG) in the control of expression of Foxp3 (a marker of T-regulatory lymphocytes, Treg), synthesis of interleukin-4 (IL-4) and interferon-gamma (IFH-γ) in lymphocytes, and secretion of indolamine-2,3-dioxygenase (IDO) by monocytes. Moreover, we evaluated the phagocytic and oxidative activities of these cells. It was shown that incubation of CG at a dose of 100 IU/ml with mononuclear cells from peripheral blood (MPC) resulted in a rise in the relative number of IL-4+CD3+CD4+T-lymphocytes whereas the number of IFN-γ+CD3+CD4+T-cells remained unaltered; the intracellular production of IFN-γ and IL-4 in the subpopulation of CD3+CD8+T-lymphocytes did not change either. In vitro, CG (10 and 100 IU/ml) significantly increased percentage of CD4+CD25 brightFoxp3+ cells and enhanced activity of indolamine-2,3-doxygenase in lipopolysaccharide-stimulated MPC. CG suppressed phagocitosis of E. coli lux+ by monocytes and simultaneously inhibited the production of active oxygen species in the reaction of spontaneous luminol-dependent chemiluminescence. Taken together, these properties of CG account for its role in the promotion of the formation of immunological tolerance during pregnancy.

The Role of Human Leukocyte Antigen G in Inducing Immune Tolerance After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4478-4478
Author(s):  
Xuan Du ◽  
Xiuli Wu ◽  
Rui Li ◽  
Zhiping Fan ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Hematopoietic Stem ◽  
Ifn Γ ◽  
High Level

Abstract Abstract 4478 Background and Objective Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is now applied widely for the treatment of hematological or non-hematological malignancies, aplastic anemia and hereditary diseases. Recently, a protocol for haploidentical allo-HSCT that combines granulocyte-colony stimulating factor (G-CSF) primed bone marrow (G-BM) and peripheral blood stem cells (G-PBSC) without in vitro T-cell depletion received great success. But the mechanism of G-CSF inducing immunotolerance in haploidentical-HSCT has not yet been clarified. Human leucocyte antigen G (HLA-G) is a nonclassical HLA class I molecule, the tolerogenic role of HLA-G is highly supported in pregnancy immunization, tumor immune escape and organ transplant. Because HLA-G closely related to immunotolerance, we investigate the role of HLA-G in inducing immune tolerance after allo-HSCT and the effects of G-CSF on the expression and secretion level of HLA-G. Methods Flow cytometry was used to detect the expression of membrane-bound HLA-G (mHLA-G) on donor peripheral blood cells (PBC) or bone marrow (BM) cells. The levels of soluble HLA-G (sHLA-G) in the plasma and bone marrow fluid were determined by enzyme-linked immunosorbent assay (ELISA). In vitro, the expression and secretion level of HLA-G in bone marrow mononuclear cells (BMMCs) and peripheral blood mononuclear cells (PBMCs) after G-CSF stimulated were detected by flow cytometry and ELISA, respectively; Separated T lymphocytes which expressed high level of HLA-G were cultured with allogeneic T lymphocytes and relative response index (RPI) was measured with MTT assay; Furthermore, separated T lymphocytes were cultured with allogeneic BMMCs and the levels of IFN-γ and IL-10 in culture supernatant were determined by ELISA. Results The mean level of mHLA-G after G-CSF mobilization in the PBC or BM cells was significantly higher than that before G-CSF mobilization (P<0.05). The level of mHLA-G or sHLA-G in BM cells was higher than that in PBC after G-CSF mobilization (P<0.05). The level of mHLA-G or sHLA-G in BMMCs or PBSCs which were stimulated by G-CSF was higher than that of the controls (P<0.05), and the level of HLA-G in BMMCs was higher than that in PBSCs. HLA-G predominant expressed in CD3+ T cells; The results of allogeneic mixed lymphocyte culture revealed that immunological function of the separated T lymphocytes which expressed high level of HLA-G was inhibited (RPI: 54.3%). The separated T lymphocytes co-cultured with allogeneic BMMCs, the levels of IFN-γ and IL-10 in culture supernatant were significantly higher than the controls (P<0.05). Conclusions HLA-G is rich in G-BM that might be interpret G-BM could induce better immunotolerance than G-PBSC. The G-CSF could regulate HLA-G expression and secretion directly. The mechanism of G-CSF inducing immunotolerance might be related to the inhibition of allogeneic T cell reactivity and the increase of IFN-γ and IL-10 secretion through HLA-G. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Gut ◽  
1998 ◽  
Vol 42 (5) ◽  
pp. 643-649 ◽  
Author(s):  
M Carol ◽  
A Lambrechts ◽  
A Van Gossum ◽  
M Libin ◽  
M Goldman ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Mucosa ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Gastrointestinal Diseases ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses.Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation.Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa.Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT).Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4.Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

scholarly journals Immunization with Brucella VirB Proteins Reduces Organ Colonization in Mice through a Th1-Type Immune Response and Elicits a Similar Immune Response in Dogs

2014 ◽  
Vol 22 (3) ◽  
pp. 274-281 ◽  
Author(s):  
Cora N. Pollak ◽  
María Magdalena Wanke ◽  
Silvia M. Estein ◽  
M. Victoria Delpino ◽  
Norma E. Monachesi ◽  
...  
Keyword(s):  
Immune Response ◽  
Mononuclear Cells ◽  
Interleukin 4 ◽  
Delayed Type Hypersensitivity ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Type Iv ◽  
Ifn Γ ◽  
Organ Colonization

ABSTRACTVirB proteins fromBrucellaspp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice fromBrucellainfection and whether this response can be induced in the dog, a natural host forBrucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with liveBrucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals uponin vitrostimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane ofBrucellaorganisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis ofB. caniswas assessedin vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization byBrucellain mice can be also elicited in dogs.

scholarly journals Polyfunctional T Lymphocytes Are in the Peripheral Blood of Donors Naturally Immune to Coccidioidomycosis and Are Not Induced by Dendritic Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 309-315 ◽  
Author(s):  
Lance Nesbit ◽  
Suzanne M. Johnson ◽  
Demosthenes Pappagianis ◽  
Neil M. Ampel
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
High Expression ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

ABSTRACT Coccidioidomycosis is a fungal infection endemic in the southwestern United States that is increasing in incidence. While cellular immunity correlates with protection from clinical illness, the precise elements of that response are undefined. Using the coccidioidal antigen preparation T27K and multiparametric flow cytometry, the in vitro frequency of polyfunctional T lymphocytes in the peripheral blood of naturally immune healthy donors and those who were nonimmune was determined. Polyfunctional CD4 lymphocytes, defined as producing intracellular interleukin 2 (IL-2), gamma interferon (IFN-γ), and tumor necrosis factor alpha simultaneously, had a frequency of 137 per 400,000 events among peripheral blood mononuclear cells (PBMC) of immune donors compared to 11 per 400,000 PBMC from nonimmune donors (P = 0.03). When monocyte-derived mature dendritic cells pulsed with T27K (mDCT27K) were used for antigen presentation, the frequency of polyfunctional CD4 T lymphocytes did not significantly increase for either group, although mDCT27K did significantly increase the concentrations of IL-2 and IFN-γ released by PBMC from nonimmune donors (P = 0.02). After in vitro stimulation with T27K, polyfunctional CD4 and CD8 lymphocytes of PBMC from immune donors had a mixture of low- and high-expression CCR7 cells, suggesting both effector and central memory, compared with predominantly high-expression CCR7 cells when PBMC were incubated with the mitogen phytohemagglutinin (P = 0.03). These data demonstrate the presence of polyfunctional T lymphocytes in the peripheral blood of individuals with coccidioidal immunity and suggest a model for the in vitro testing of vaccine candidates for coccidioidomycosis.

scholarly journals The priming role of dendritic cells on the cancer cytotoxic effects of cytokine-induced killer cells

2019 ◽  
Vol 22 (2) ◽  
pp. 196-212
Author(s):  
Binh Thanh Vu ◽  
Nguyet Thi-Anh Tran ◽  
Tuyet Thi Nguyen ◽  
Quyen Thanh-Ngoc Duong ◽  
Phong Minh Le ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mononuclear Cells ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
In Vitro Cultivation ◽  
Killer Cells ◽  
Flow Cytometry Data ◽  
Cik Cells ◽  
Ifn Γ

Introduction: In vitro cultivation of DCs and cytokine-induced killer cells (CIK cells) - a special phenotype of T lymphocyte populations — for cancer treatment has gained significant research interest. The goal of this study is to understand whether the priming from DCs helps CIK cells to exert their toxic function and kill the cancer cells. Methods: In this research, DCs were differentiated from mononuclear cells in culture medium supplemented with Granulocyte-macrophage colony-stimulating factor (GM-CSF), and Interleukin-4 (IL-4), and were induced to mature with cancer cell antigens. Umbilical cord blood mononuclear cells were induced into CIK cells by Interferon-γ (IFN-γ), anti-CD3 antibody and IL-2. After 4-day exposure (with DC:CIK = 1:10), DCs and CIK cells interacted with each other. Results: Indeed, DCs interacted with and secreted cytokines that stimulated CIK cells to proliferate up to 133.7%. In addition, DC-CIK co-culture also stimulated strong expression of IFN-γ. The analysis of flow cytometry data indicated that DC-CIK co-culture highly expressed Granzyme B (70.47% ± 1.53, 4 times higher than MNCs, twice higher than CIK cells) and CD3+CD56+ markers (13.27% ± 2.73, 13 times higher than MNCs, twice higher than CIK cells). Particularly, DC-CIK co-culture had the most specific lethal effects on cancer cells after 72 hours. Conclusion: In conclusion, co-culture of DCs and CIK cells is capable of increasing the expression of CIK-specific characteristics and CIK toxicity on cancer cells.    

scholarly journals Heterogeneity of Wild Leishmania major Isolates in Experimental Murine Pathogenicity and Specific Immune Response

2001 ◽  
Vol 69 (8) ◽  
pp. 4906-4915 ◽  
Author(s):  
C. Kébaı̈er ◽  
H. Louzir ◽  
M. Chenik ◽  
A. Ben Salah ◽  
K. Dellagi
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 4 ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Tunisian Patients ◽  
Ifn Γ

ABSTRACT Virulence variability was investigated by analyzing the experimental pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve strains were isolated from Tunisian patients with zoonotic cutaneous leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind footpad with 2 × 106 amastigotes of the various isolates, and lesion progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma interferon (IFN-γ) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We show that disease progression induced by different L. major isolates was largely heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-γ in vitro at week 5 postinfection as well as higher levels of early IL-4 mRNA in the lymph node draining the inoculation site at 16 h postinfection. These results suggest that L. major isolates from the field may differ in virulence, which influences the course of the disease induced in mice and the type of immune response elicited by the infected host.

scholarly journals Up-Regulation of CD40 Ligand and Induction of a Th2 Response in Children Immunized with Pneumococcal Polysaccharide Vaccines

2001 ◽  
Vol 8 (2) ◽  
pp. 233-240 ◽  
Author(s):  
Lily E. Leiva ◽  
Boyd Butler ◽  
James Hempe ◽  
Alejandro P. Ortigas ◽  
Ricardo U. Sorensen
Keyword(s):  
Mrna Expression ◽  
Mononuclear Cells ◽  
Cd40 Ligand ◽  
Interleukin 4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th2 Response ◽  
Polysaccharide Antigens ◽  
Ifn Γ ◽  
Antibody Levels

ABSTRACT We wished to determine whether pneumococcal polysaccharide antigens induce mRNA expression of CD40 ligand (CD40L) and Th1 or Th2 cytokines in unimmunized individuals in vitro and whether immunization with the 23-valent pneumococcal polysaccharide vaccine induces changes in CD40L and cytokine mRNA expression. Children with recurrent respiratory infections were studied before and 4 to 6 weeks after receiving the pneumococcal vaccine. One patient who failed to respond to the polysacharide vaccine subsequently received a single dose of the experimental 7-valent pneumococcal conjugate vaccine. Unimmunized healthy adults were included as controls. Quantification of mRNA expression of CD40L, interleukin-4 (IL-4), IL-12p40, and gamma interferon (IFN-γ) was performed by reverse transcription-PCR and enzyme-linked immunosorbent assay (ELISA)-PCR with resting and stimulated peripheral blood mononuclear cells. Serum immunoglobulin G (IgG) anti pneumococcal antibody levels were measured by ELISA. The results showed a significant increase in the expression of mRNAs for CD40L and IL-4, but not IL-12p40 or IFN-γ, in stimulated cultures from unimmunized individuals. CD40L and IL-4 mRNA expression was significantly higher in postimmunization than in preimmunization samples stimulated with the individual pneumococcal serotypes. These results suggest that pneumococcal polysaccharide antigens specifically up-regulate CD40L expression and induce a Th2 response in vitro which parallels the increase in IgG antipneumococcal antibody levels in serum.

scholarly journals Mechanisms of T-Lymphocyte Accumulation during Experimental Pleural Infection Induced by Mycobacterium bovis BCG

2008 ◽  
Vol 76 (12) ◽  
pp. 5686-5693 ◽  
Author(s):  
Mariana C. Souza ◽  
Carmen Penido ◽  
Maria F. S. Costa ◽  
Maria Graças Henriques
Keyword(s):  
T Lymphocytes ◽  
Mycobacterium Bovis ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Pleural Space ◽  
T Lymphocyte Proliferation ◽  
Pleural Infection ◽  
Ifn Γ

ABSTRACT Tuberculous pleurisy is a frequent extrapulmonary manifestation characterized by accumulation of fluid and inflammatory cells in the pleural space. Here, we investigated the mechanisms of T-lymphocyte accumulation in the pleural space by using a murine model of pleurisy induced by Mycobacterium bovis BCG. Intrathoracic (i.t.) injection of BCG (4.5 × 105 bacteria/cavity) induced accumulation of T lymphocytes in the pleural cavities of C57BL/6 mice. We observed the presence of CFU in pleural washes conducted 1, 2, 3, 7, and 15 days after pleurisy induction. Pretreatment with fucoidan inhibited T-lymphocyte accumulation at 1 day, but not at 15 days, after BCG-induced pleurisy. Accordingly, adoptive transfer of fluorescein isothiocyanate-labeled blood mononuclear cells to infected mice showed that T lymphocytes migrated into the pleural cavity 1 day (but not 15 days) after BCG injection. Cell-free pleural wash fluids recovered from mice 1 day after BCG i.t. stimulation (day 1 BCG-PW), but not day 7 or day 15 BCG-PW, induced in vitro T-cell transmigration, which was dependent on L-, P-, and E-selectins. In contrast, day 7 BCG-PW (but not day 1 BCG-PW) induced in vitro T-lymphocyte proliferation via interleukin-2 (IL-2) and gamma interferon (IFN-γ). Accordingly, in vivo IL-2 or IFN-γ neutralization abolished T-lymphocyte accumulation 7 days after pleurisy induction. Our results demonstrate that pleural infection induced by BCG leads to T-lymphocyte accumulation in two waves. The acute phase depends on selectin-mediated migration, while the second wave of T-lymphocyte accumulation seems to depend on a local proliferation induced by cytokines produced in situ.

scholarly journals The role of peripheral immunological tolerance in the pathogenesis of systemic lupus erythematosus

2016 ◽  
Author(s):  
Αικατερίνη-Κυριακή Βλάχου
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Reactive Oxygen ◽  
Immunological Tolerance ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Ifn Γ

Παρά την πολυπλοκότητα της αιτιοπαθογένειας των αυτοάνοσων νοσημάτων, της πλούσιας ποικιλίας των κλινικών συμπτωμάτων μεταξύ ασθενών και τη διαφορετική ανταπόκριση των ασθενών σε κοινές συμπτωματικές θεραπείες, υπάρχει μια κοινή αρχή: τα αυτοάνοσα νοσήματα αναπτύσσονται εξαιτίας της απώλειας της ανοσολογικής ανοχής στα αυτοαντιγόνα. Συνεπώς είναι αναγκαίο να διαλευκάνουμε τις γενεσιουργές αιτίες στις οποίες οφείλεται η αδυναμία ελέγχου και διατήρησης της ανοσολογικής ανοχής. Η κατανόηση των σχετικών υπεύθυνων μοριακών μηχανισμών θα προσφέρει την ευκαιρία ανάπτυξης στοχευμένων, έγκαιρων και αποτελεσματικότερων θεραπειών με κοινά οφέλη για ένα μεγάλο εύρος αυτοάνοσων νοσημάτων. Τα κατασταλτικά κύτταρα μυελικής προέλευσης (MDSCs) είναι ένα ετερογενής πληθυσμός μυελικών, ατελώς διαφοροποιημένων κυττάρων με ανοσορυθμιστικές ιδιότητες, τα οποία πρόσφατα έχουν συγκεντρώσει το ενδιαφέρον της επιστημονικής κοινότητας. Αποτελούνται από δύο υποπληθυσμούς κυττάρων, τα κοκκιοκυτταρικά (G-MDSCs) και τα μονοκυτταρικά (M-MDSCs). Το κύριο χαρακτηριστικό των MDSCs είναι ότι μπορούν να καταστείλουν τις ανοσολογικές αποκρίσεις των Τ λεμφοκυττάρων. Στην παρούσα ερευνητική εργασία, εστιάσαμε στο ρόλο των MDSCs στην παθογένεια του Συστηματικού Ερυθηματώδη Λύκου (ΣΕΛ). Ο ΣΕΛ είναι ένα συστεμικό αυτοάνοσο νόσημα, όπου η επιμένουσα απώλεια των ρυθμιστικών μηχανισμών διατήρησης της ανοσολογικής ανοχής συμβάλει στην παθογένεια της ασθένειας και την εγκαθίδρυση χρόνιας φλεγμονής. Για το λόγο αυτό, σχεδιάσαμε να εξετάσουμε το ρόλο των MDSC ρυθμιστικών κυττάρων στο ΣΕΛ, χρησιμοποιώντας το ζωικό μοντέλο NZB/W F1, ποντίκια τα οποία αυθόρμητα αναπτύσσουν ένα φαινότυπο παρόμοιο με του ΣΕΛ στον άνθρωπο. Με την εργασία αυτή δείχνουμε πως τα CD11bhighGr-1+ MDSCs ανιχνεύονται σε χαμηλά επίπεδα στα NZB/W F1 ποντίκια, τόσο στο υποκλινικό όσο και στο κλινικό στάδιο της νόσου. Αυτό κυρίως οφείλεται στη μειωμένη συχνότητα εμφάνισης των CD11bhighLy6G+ G-MDSCs στο μυελό των οστών και στα περιφερικά λεμφικά όργανα των ποντικιών με τη νόσο. Ο μειωμένος αριθμός των CD11bhighLy6G+ G-MDSC συνοδεύονται και από την ελαττωματική λειτουργία τους όσον αφορά στην in vitro καταστολή των CD4+ T λεμφοκυττάρων. Ενδιαφέρον προκαλεί ότι τα G-MDSC του λύκου όχι μόνο δεν μπορούν να καταστείλουν τα CD4+ T λεμφοκύτταρα, αλλά αντίθετα προκαλούν τον πολλαπλασιασμό κα την ενεργοποίηση τους. Σημαντικό είναι το εύρημα μας ότι τα CD11bhighLy6G+ G-MDSCs είναι μειωμένα στο λύκο εξαιτίας της αυξημένης απελευθέρωσης εξωκυττάριων παγίδων (Extracellular Traps, ETs) που προκαλείται από το φλεγμονώδες περιβάλλον του λύκου. Η αυξημένη απελευθέρωση των ETs (ΕTωση) εξαρτάται από την παραγωγή αντιδραστικών ριζών οξυγόνου (Reactive Oxygen Speces, ROS), η οποία επίσης προάγεται από τις φλεγμονώδεις ιδιότητες του περιβάλλοντος του λύκου. Τέλος, δείχνουμε ότι τρεις από τις εμπλουτισμένες κυτταροκίνες στο περιβάλλον του λύκου, οι IFN-α, IFN-γ και IL-6 έχουν την ικανότητα να επάγουν την ETωση στα κοκκιοκυτταρικά κύτταρα. Συμπερασματικά, τα δεδομένα μας αποδεικνύουν τη μειωμένη έκπτυξη των G-MDSC κυττάρων στο μικροπεριβάλλον του λύκου εξαιτίας του σχηματισμού των ETs, μια διαδικασία που αποτελεί ένα καινοφανή τύπο κυτταρικού θανάτου. Επιπλέον, παρέχουμε στοιχεία που υποστηρίζουν τη μεσολάβηση των ROS στο φαινόμενο αυτό. Η εξάλειψη των G-MDSC ενδεχομένως να έχει ως αποτέλεσμα την ελαττωματική ρύθμιση των ανοσολογικών αποκρίσεων συμβάλλοντας έτσι στην εξέλιξη της ασθένειας. Τα ευρήματά μας παρέχουν νέα στοιχεία στην κατανόηση της παθογένειας του ΣΕΛ και θα μπορούσε να συνεισφέρει στην ανάπτυξη νέων θεραπευτικών μεθόδων.

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