Anti-IL-16 therapy reduces CD4+ T-cell infiltration and improves paralysis and histopathology of relapsing EAE

2005 ◽  
Vol 79 (5) ◽  
pp. 680-693 ◽  
Author(s):  
Dusanka S. Skundric ◽  
Rujuan Dai ◽  
Vaagn L. Zakarian ◽  
Denise Bessert ◽  
Robert P. Skoff ◽  
...  
Keyword(s):  
T Cell ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration

Abstract 760: Heme Oxygenase-1 expression in Dendritic Cells determines the Outcome of Transplantation Arteriosclerosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Annemarie Noordeloos ◽  
Elza van Deel ◽  
Denise Hermes ◽  
Maarten L Simoons ◽  
Dirk J Duncker ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Heme Oxygenase ◽  
T Cell Activation ◽  
Neointimal Hyperplasia ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Heme Oxygenase 1 ◽  
T Cell Infiltration ◽  
Mhcii Expression

Introduction: Although expression of heme oxygenase-1 (HO1) attenuates transplantation arteriosclerosis, the mechanism by which HO1 exerts its protective effect remains unclear. We studied the effect of HO1-deficient vs. wildtype (WT) dendritic cells (DCs) on the T-cell priming response and outcome in a murine transplant arteriosclerosis model. Methods: At day 0 C57bl6 mice received either WT (n=6) or HO1-knockout DCs (n=6) pre-sensitized with Balb/c splenocytes lysate to accelerate the development of arteriosclerosis. At day 10 an aorta segment from Balb/c mice was transplanted into the carotid artery position of C57Bl6 mice.14 days after transplantation allografts were excised and processed for immunohistochemical analysis. Results: HO1-deficient DCs significantly increased neointimal hyperplasia as compared to WT DCs (116995 vs. 46114μm 2 P<0.05) and incidence of intima formation (83 vs. 50% in WT DC). HO1 deficient DCs also increased medial thickeness (15936 vs.12034 μm 2 P<0.05) and intimal VSMCs content (76 vs. 46% P<0.05) and resulted in more prominent medial cell infiltration (461μm 2 vs. 232μm 2 P<0.05). Although HO1 deficient and WT DCs could be detected in allografts, HO1-nullizygous DCs induced an increase in CD4+ T-cell infiltration (9.5 vs. 0.1% in WT P<0.05) concomitant to a decrease of CD8+ T cell infiltration (8 vs.14%, P<0.05). In line with these observations Affymetrix microarray analysis confirmed that HO1 deletion in DCs was associated with a significant downregulation of MHCII-H2A expression (associated with CD4+T-cell activation) and induction of inhibitors of MHCII expression (including IK protein) whereas MHC I expression remained unchanged. Conclusions: HO1 expression in dendritic cells increases vascular cell infiltration with a higher CD8+/CD4+ T-cell ratio by stabilizing MHCII expression in vascular allografts resulting in inhibition of neointima formation and hence improved allograft survival.

Both Stat5a and Stat5b are required for antigen-induced eosinophil and T-cell recruitment into the tissue

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1370-1377 ◽  
Author(s):  
Shin-ichiro Kagami ◽  
Hiroshi Nakajima ◽  
Kotaro Kumano ◽  
Kotaro Suzuki ◽  
Akira Suto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Specific Ige ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Cell Recruitment ◽  
Eosinophil Recruitment ◽  
Airway Eosinophilia ◽  
T Cell Infiltration

Antigen-induced eosinophil recruitment into the airways of sensitized mice is mediated by CD4+ T cells and their cytokines, especially IL-5. In this study, we found that the antigen-induced airway eosinophilia was diminished in Stat5a-deficient (Stat5a−/−) mice and Stat5b-deficient (Stat5b−/−) mice. We also found that antigen-induced CD4+ T-cell infiltration and IL-5 production in the airways were diminished in Stat5a−/− mice and Stat5b−/− mice. Moreover, antigen-induced proliferation of splenocytes was diminished in Stat5a−/− mice and Stat5b−/− mice, suggesting that the generation of antigen-primed T cells may be compromised in Stat5a−/−mice and Stat5b−/− mice and this defect may account for the diminished antigen-induced T-cell infiltration into the airways. Interestingly, IL-4 and IL-5 production from anti-CD3–stimulated splenocytes was diminished in Stat5a−/− mice and Stat5b−/− mice. However, antigen-specific IgE and IgG1 production was diminished in Stat5a−/− mice but not in Stat5b−/− mice, whereas antigen-specific IgG2a production was increased in Stat5a−/− mice, suggesting the enhanced Th1 responses in Stat5a−/− mice. Finally, we found that eosinophilopoiesis induced by the administration of recombinant IL-5 was also diminished in Stat5a−/− mice and Stat5b−/− mice. Together, these results indicate that both Stat5a and Stat5b are essential for induction of antigen-induced eosinophil recruitment into the airways and that the defects in antigen-induced eosinophil recruitment in Stat5a−/− mice and Stat5b−/− mice result from both impaired IL-5 production in the airways and diminished IL-5 responsiveness of eosinophils.

scholarly journals Major Histocompatibility Complex Class II Expression by Intrinsic Renal Cells Is Required for Crescentic Glomerulonephritis

1998 ◽  
Vol 188 (3) ◽  
pp. 597-602 ◽  
Author(s):  
Shuo Li ◽  
Christian Kurts ◽  
Frank Köntgen ◽  
Stephen R. Holdsworth ◽  
Peter G. Tipping
Keyword(s):  
T Cell ◽  
Renal Injury ◽  
Crescentic Glomerulonephritis ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Renal Cells ◽  
Chimeric Mice ◽  
Mhc Ii ◽  
T Cell Infiltration ◽  
Histocompatibility Complex

The requirement for major histocompatibility complex class II (MHC II) to initiate immune renal injury was studied in a murine model of CD4+ T cell–dependent crescentic glomerulonephritis (GN). C57BL/6 (MHC II+/+) mice developed crescentic GN with glomerular CD4+ T cell infiltration and renal injury, in response to a nephritogenic antigen (sheep globulin) planted on their glomerular basement membrane. MHC II–deficient C57BL/6 mice (MHC II−/−) did not develop crescentic GN, CD4+ T cell infiltration, or injury, indicating that this form of immune glomerular injury is MHC II dependent. The requirement for MHC II expression by intrinsic renal cells was studied in chimeric mice, which expressed MHC II on bone marrow–derived cells and in the thymus, but not in the kidneys. These chimeric mice had normal T and B cell populations and MHC II expression in their spleens and lymph nodes and developed an immune response to systemically and cutaneously administered sheep globulin. However, they did not develop crescentic GN, CD4+ T cell infiltration, or renal injury in response to the sheep globulin planted in their glomeruli. These studies demonstrate that interaction of CD4+ T cells with intrinsic renal cells expressing MHC II is required for development of cell-mediated immune renal injury.

scholarly journals The autoimmune encephalitis-related cytokine TSLP in the brain primes neuroinflammation by activating the JAK2-NLRP3 axis

2021 ◽  
Author(s):  
Xueyuan Yu ◽  
Jiajia Lv ◽  
Jun Wu ◽  
Yong Chen ◽  
Fei Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Brain ◽  
Autoimmune Encephalitis ◽  
Cell Number ◽  
Janus Kinase ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
The Brain ◽  
Nlrp3 Expression

Abstract NLRP3 inflammasome hyperactivation contributes to neuroinflammation in autoimmune disorders, but the underlying regulatory mechanism remains to be elucidated. We demonstrate that compared with wild-type (WT) mice, mice lacking thymic stromal lymphopoietin (TSLP) receptor (TSLPR) (Tslpr -/- mice) exhibit a significantly decreased experimental autoimmune encephalitis (EAE) score, reduced CD4 + T cell infiltration, and restored myelin basic protein (MBP) expression in the brain after EAE induction by myelin oligodendrocyte glycoprotein35-55 (MOG35-55). TSLPR signals through Janus kinase (JAK)2, but not JAK1 or JAK3, to induce NLRP3 expression, and Tslpr -/- mice with EAE show decreased JAK2 phosphorylation and NLRP3 expression in the brain. JAK2 inhibition by ruxolitinib mimicked loss of TSLPR function in vivo and further decreased TSLP expression in the EAE mouse brain. The NLRP3 inhibitor MCC950 decreased CD4 + T cell infiltration, restored MBP expression, and decreased IL-1β and TSLP levels, verifying the proinflammatory role of NLRP3. In vitro experiments using BV-2murine microglia revealed that TSLP directly induced NLRP3 expression, phosphorylation of JAK2 but not JAK1orJAK3, and IL-1β release, which were markedly inhibited by ruxolitinib. Furthermore, EAE induction led to an increase in the Th17 cell number, a decrease in the regulatory T (Treg) cell number in the blood, and an increase in the expression of the cytokine IL-17A in the WT mouse brain, which was drastically reversed in Tslpr -/- mice. In addition, ruxolitinib suppressed the increase in IL-17A expression in the EAE mouse brain. These findings identify TSLP as a prospective target for treating JAK2-NLRP3 axis-associated autoimmune inflammatory disorders.

scholarly journals The clinicopathological features of extensive small intestinal CD4 T cell infiltration

Gut ◽  
1999 ◽  
Vol 45 (5) ◽  
pp. 662-667 ◽  
Author(s):  
F Carbonnel ◽  
H d'Almagne ◽  
A Lavergne ◽  
C Matuchansky ◽  
J C Brouet ◽  
...  
Keyword(s):  
T Cell ◽  
Clinicopathological Features ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Small Intestinal

Rat acute GvHD is Th1 driven and characterized by predominant donor CD4 + T-cell infiltration of skin and gut

2017 ◽  
Vol 50 ◽  
pp. 33-45.e3 ◽  
Author(s):  
Margherita Boieri ◽  
Pranali Shah ◽  
Dasaradha Jalapothu ◽  
Olena Zaitseva ◽  
Lutz Walter ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Gvhd ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
T Cell Infiltration

scholarly journals Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells.

1993 ◽  
Vol 177 (2) ◽  
pp. 573-576 ◽  
Author(s):  
I Iwamoto ◽  
H Nakajima ◽  
H Endo ◽  
S Yoshida
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interferon Gamma ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Eosinophil Infiltration ◽  
Ifn Gamma ◽  
Eosinophil Recruitment ◽  
T Cell Infiltration

We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and interleukin 5. To determine whether interferon gamma (IFN-gamma) regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of recombinant (r) murine IFN-gamma and of anti-IFN-gamma monoclonal antibody (mAb) on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. The intraperitoneal administration of rIFN-gamma prevented antigen-induced eosinophil infiltration in the trachea of sensitized mice. The administration of rIFN-gamma also decreased antigen-induced CD4+ T cell but not CD8+ T cell infiltration in the trachea. On the other hand, pretreatment with anti-IFN-gamma mAb enhanced antigen-induced eosinophil and CD4+ T cell infiltration in the trachea. These results indicate that IFN-gamma regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4+ T cell infiltration.

scholarly journals Agonism of Prostaglandin E2 Receptor 4 Ameliorates Tubulointerstitial Injury in Nephrotoxic Serum Nephritis in Mice

2021 ◽  
Vol 10 (4) ◽  
pp. 832
Author(s):  
Ida Aringer ◽  
Katharina Artinger ◽  
Corinna Schabhüttl ◽  
Thomas Bärnthaler ◽  
Agnes A. Mooslechner ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Complex ◽  
Cd4 T Cell ◽  
Cell Infiltration ◽  
Tubular Cells ◽  
Nephrotoxic Serum Nephritis ◽  
T Cell Infiltration ◽  
Ep4 Receptor

Selectively targeting the E-type prostanoid receptor 4 (EP4) might be a new therapeutic option in the treatment of glomerulonephritis (GN), since the EP4 receptor is expressed on different immune cells, resident kidney cells, and endothelial cells, which are all involved in the pathogenesis of immune-complex GN. This study aimed to evaluate the therapeutic potential and to understand the mode of action of EP4 agonist in immune-complex GN using the murine model of nephrotoxic serum nephritis (NTS). In vivo, NTS mice were treated two times daily with two different doses of an EP4 agonist ONO AE1-329 or vehicle for 14 days total. The effect of PGE2 and EP4 agonism and antagonism was tested on murine distal convoluted tubular epithelial cells (DCT) in vitro. In vivo, the higher dose of the EP4 agonist led to an improved NTS phenotype, including a reduced tubular injury score and reduced neutrophil gelatinase-associated lipocalin (NGAL) and blood urea nitrogen (BUN) levels. EP4 agonist treatment caused decreased CD4+ T cell infiltration into the kidney and increased proliferative capacity of tubular cells. Injection of the EP4 agonist resulted in dose-dependent vasodilation and hypotensive episodes. The low-dose EP4 agonist treatment resulted in less pronounced episodes of hypotension. In vitro, EP4 agonism resulted in cAMP production and increased distal convoluted tubular (DCT) proliferation. Taken together, EP4 agonism improved the NTS phenotype by various mechanisms, including reduced blood pressure, decreased CD4+ T cell infiltration, and a direct effect on tubular cells leading to increased proliferation probably by increasing cAMP levels.

Sign in / Sign up

Export Citation Format

Share Document