scholarly journals Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition.

1998 ◽  
Vol 9 (12) ◽  
pp. 2272-2282 ◽  
Author(s):  
M J Penny ◽  
R A Boyd ◽  
B M Hall
Keyword(s):  
T Cells ◽  
Mycophenolate Mofetil ◽  
Interferon Gamma ◽  
Cd8 T Cells ◽  
Membranous Nephropathy ◽  
Interleukin 4 ◽  
Cytokine Mrna ◽  
Necrosis Factor Alpha ◽  
Heymann Nephritis ◽  
Cytokine Inhibition

The effect of mycophenolate mofetil (MMF) was examined in active Heymann nephritis (HN), an animal model of human membranous nephropathy. HN was induced in Lewis rats with Fx1A/complete Freund's adjuvant (CFA), and controls only received CFA. The induction of HN was prevented by MMF (30 mg/kg per d) from 0 to 4 wk after immunization. Proteinuria was not different in CFA controls up to 16 wk, and was significantly less than in untreated HN from 6 wk onward. Serum anti-Fx1A antibody (Ab) levels and glomerular Ig deposition were suppressed during therapy. The interstitial infiltrate of alphabetaTCR+, CD4+ and CD8+ T cells, natural killer cells, and macrophages (mphi) observed in untreated HN at 8 wk was absent from rats treated from 0 to 4 wk with MMF. Semiquantitative reverse transcription-PCR for renal mononuclear cell cytokine mRNA at 8 wk demonstrated that MMF from 0 to 4 wk prevented the increased expression of Th1 (interferon-gamma, lymphotoxin), Th2 (interleukin-4), and mphi (tumor necrosis factor-alpha) cytokines identified in untreated HN. In lymph node draining sites of immunization, MMF limited both enlargement and the increased proportion of CD3+, CD4+, and CD8+ T cells observed in untreated HN and CFA controls. MMF suppressed Th2 (interleukin-4) but not Th1 (interferon-gamma, lymphotoxin) cytokine mRNA expression in lymph nodes. MMF from 4 to 8, 6 to 12, or 10 to 14 wk did not prevent proteinuria, serum anti-Fx1A Ab, or glomerular IgG deposition when compared with untreated HN. This study showed that MMF from 0 to 4 wk prevented the induction of HN and was associated with preferential suppression of Th2 cytokines. This therapy may prove useful in human idiopathic membranous nephropathy.

scholarly journals Permanent CD8+ T Cell Depletion Prevents Proteinuria in Active Heymann Nephritis

1998 ◽  
Vol 188 (10) ◽  
pp. 1775-1784 ◽  
Author(s):  
Mark J. Penny ◽  
Rochelle A. Boyd ◽  
Bruce M. Hall
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Membranous Nephropathy ◽  
Cd8 T Cell ◽  
Cell Depletion ◽  
Cytotoxic T Cell ◽  
Glomerular Injury ◽  
T Cell Depletion ◽  
Heymann Nephritis

Active Heymann nephritis (HN) is a rat model of human idiopathic membranous nephropathy in which injury is thought to be mediated by membrane attack complex of complement (MAC) activated by antibody (Ab) to glomerular epithelial cells. Recent work has shown that HN develops in C6-deficient rats which cannot assemble MAC, and that infiltration of activated cytotoxic CD8+ T cells and macrophages into glomeruli coincides with proteinuria. This study examined the role of CD8+ T cells in mediating glomerular injury in HN by permanent CD8+ cytotoxic T cell depletion via adult thymectomy (ATx) and anti-CD8 mAb. Groups of rats were depleted of CD8+ T cells either before immunization for HN or 6 wk after immunization when Ab responses and glomerular IgG deposition were well established. These were compared with groups of HN, ATx/HN, and complete Freund's adjuvant (CFA) controls. Neither group of CD8+ T cell–depleted rats developed proteinuria, although there was normal development and deposition of Ab. CD8+ T cell–depleted rats developed neither T cell or macrophage infiltrates nor their effector cytokines, which are present in glomeruli of rats with HN. Examination of lymph node (LN) draining sites of immunization showed these findings were not explained by altered immune events within these LNs. It was concluded that CD8+ cytotoxic T cells are essential to the mediation of glomerular injury in HN and may be relevant to the pathogenesis and treatment of membranous nephropathy.

scholarly journals Enterovirus 71 infection increases expression of interferon-gamma-inducible protein 10 which protects mice by reducing viral burden in multiple tissues

2013 ◽  
Vol 94 (5) ◽  
pp. 1019-1027 ◽  
Author(s):  
Fang-Hsiu Shen ◽  
Chia-Chun Tsai ◽  
Li-Chiu Wang ◽  
Kung-Chao Chang ◽  
Yuk-Ying Tung ◽  
...  
Keyword(s):  
T Cells ◽  
Interferon Gamma ◽  
Cd8 T Cells ◽  
Enterovirus 71 ◽  
Gamma Interferon ◽  
Ev71 Infection ◽  
Asia Pacific ◽  
Virus Clearance ◽  
Viral Burden ◽  
Inducible Protein

Enterovirus 71 (EV71) infection has induced fatal encephalitis in thousands of young children in the Asia–Pacific region over the last decade. EV71 infection continues to cause serious problems in areas with outbreaks, because vaccines and antiviral therapies are not available. Lymphocytes are present in the brains of infected patients and mice, and they protect mice from infection by decreasing the viral burden. The chemokines responsible for recruiting lymphocytes to infected organs are yet to be identified. Among the lymphocyte chemokines detected, high levels of interferon-gamma-inducible protein-10 (IP-10) are found in the plasma and cerebral spinal fluid of patients with brainstem encephalitis as compared with the levels of a monokine induced by gamma interferon (Mig). Using a murine model to investigate the induction of IP-10 by EV71 infection, we observed that EV71 infection significantly enhanced IP-10 protein expression in the serum and brain, with kinetics similar to viral titres in the blood and brain. Brain neurons of infected mice expressed IP-10. Using wild-type mice and IP-10 gene knockout mice to investigate the role of IP-10 in EV71 infection, we found that IP-10 deficiency significantly reduced levels of Mig in serum, and levels of gamma interferon and the number of CD8 T cells in the mouse brain. Absence of IP-10 significantly increased the mortality of infected mice by 45 %, with slow virus clearance in several vital tissues. Our observations are consistent with a model where EV71 infection boosts IP-10 expression to increase gamma interferon and Mig levels, infiltration of CD8 T cells, virus clearance in tissues and the survival of mice.

Interleukin-4 levels in peripheral blood CD8+ T cells in mild atopic asthmatics

1997 ◽  
Vol 56 ◽  
pp. 413
Author(s):  
L. Stanciu ◽  
J. Shute ◽  
C. Promwong ◽  
S. Holgate ◽  
R. Djukanovic
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Interleukin 4

Interleukin 4 (BSF-1) induces growth in resting murine CD8 T cells triggered via cross-linking of T3 cell surface structures

1988 ◽  
Vol 18 (5) ◽  
pp. 767-772 ◽  
Author(s):  
Thomas Miethke ◽  
Ruth Schmidberger ◽  
Klaus Heeg ◽  
Steven Gillis ◽  
Hermann Wagner
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
Cd8 T Cells ◽  
Surface Structures ◽  
Interleukin 4 ◽  
Cross Linking ◽  
Cell Surface Structures

Antigen-specific CD8+ T cells inhibit IgE responses and interleukin-4 production by CD4+ T cells

1997 ◽  
Vol 27 (10) ◽  
pp. 2657-2665 ◽  
Author(s):  
Beverly J. Holmes ◽  
Paul A. Macary ◽  
Alistair Noble ◽  
D. Michael Kemeny
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Interleukin 4

scholarly journals Therapeutic activity of multiple common γ-chain cytokine inhibition in acute and chronic GVHD

Blood ◽  
2015 ◽  
Vol 125 (3) ◽  
pp. 570-580 ◽  
Author(s):  
Anne-Kathrin Hechinger ◽  
Benjamin A. H. Smith ◽  
Ryan Flynn ◽  
Kathrin Hanke ◽  
Cameron McDonald-Hyman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Cd8 T Cells ◽  
Granzyme B ◽  
Chronic Gvhd ◽  
Therapeutic Activity ◽  
Cytokine Inhibition ◽  
Key Points ◽  
The Common

Key Points Monoclonal antibody blockade of the common γ chain attenuates acute and chronic GVHD. Common γ-chain cytokines increase granzyme B levels in CD8 T cells, which are reduced upon CD132 blockade in vivo.

scholarly journals CD8+ T-Cells Expressing Interferon Gamma or Perforin Play Antagonistic Roles in Heart Injury in Experimental Trypanosoma Cruzi-Elicited Cardiomyopathy

2012 ◽  
Vol 8 (4) ◽  
pp. e1002645 ◽  
Author(s):  
Jaline Coutinho Silverio ◽  
Isabela Resende Pereira ◽  
Márcio da Costa Cipitelli ◽  
Nathália Ferreira Vinagre ◽  
Maurício Martins Rodrigues ◽  
...  
Keyword(s):  
T Cells ◽  
Trypanosoma Cruzi ◽  
Interferon Gamma ◽  
Cd8 T Cells ◽  
Heart Injury
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