scholarly journals T cell lessons from the rheumatoid arthritis synovium SCID mouse model: CD3-rich synovium lacks response to CTLA-4ig but is successfully treated by interleukin-17 neutralization

2012 ◽  
Vol 64 (6) ◽  
pp. 1762-1770 ◽  
Author(s):  
Marije I. Koenders ◽  
Renoud J. Marijnissen ◽  
Leo A. B. Joosten ◽  
Shahla Abdollahi-Roodsaz ◽  
Franco E. Di Padova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Mouse Model ◽  
Scid Mouse ◽  
Rheumatoid Arthritis Synovium ◽  
Interleukin 17 ◽  
Scid Mouse Model

scholarly journals The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) mouse model for rheumatoid arthritis

2008 ◽  
Vol 68 (1) ◽  
pp. 124-129 ◽  
Author(s):  
A Knedla ◽  
B Riepl ◽  
S Lefèvre ◽  
S Kistella ◽  
J Grifka ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mouse Model ◽  
Scid Mouse ◽  
Severe Combined Immunodeficiency ◽  
Protective Effects ◽  
Combined Immunodeficiency ◽  
Human Cartilage ◽  
Osmotic Minipumps ◽  
Osmotic Pumps ◽  
Scid Mouse Model

Objectives:The viral gene transfer of interleukin 1 receptor antagonist (IL1ra) and interleukin 10 (IL10) into rheumatoid arthritis (RA) synovial fibroblasts (RASFs) has shown protective effects on cartilage destruction in the severe combined immunodeficiency (SCID) mouse model of RA. Nevertheless, side effects of viral transduction are possible and a number of cytokines or cytokine inhibitors are not available encoded in viral vehicles. As the production of viruses coding for bioactive proteins is cost and time intensive, we established an in vivo long-term release model using osmotic minipumps in the SCID mouse model for RA.Methods:Isolated RASFs were cultured for four passages and coimplanted together with human cartilage and an Alzet osmotic miniature pump model 2004, containing 200 μl of IL10 and IL1ra for 40 days in SCID mice. Implants were removed after 40 days and evaluated histologically. The actual rates of IL10 and IL1ra in murine serum were measured by ELISA.Results:Release of IL10 and IL1ra by the pumps was effective as both could be measured in significant amounts in the serum of the mice. IL10 and IL1ra release showed protective effects towards the coimplanted cartilage, similar to the adenovirally IL10/IL1ra-transduced RASFs. The mean (SD) invasion scores for the implants with the osmotic pumps were: invasion 0.7 (0.5), degradation 0.5 (0.3) (all parameters significant vs controls, p<0.05).Conclusions:The results demonstrate that the combination of osmotic pumps with the SCID mouse model for RA can be used as approach for application and evaluation of cartilage-protective molecules. Furthermore, the effect of cartilage-protective cytokines is independent of the type of application.

scholarly journals T cell lessons from the RA synovium SCID mouse model: synovial tissue rich in CD3 T cells lacks response to CTLA4-Ig, but is successfully treated with anti-IL-17 antibodies

2011 ◽  
Vol 70 (Suppl 2) ◽  
pp. A73-A74
Author(s):  
M. I. Koenders ◽  
R. J. Marijnissen ◽  
S. Abdollahi-Roodsaz ◽  
F. E. D. Padova ◽  
A. H. Boots ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mouse Model ◽  
Synovial Tissue ◽  
Scid Mouse ◽  
Scid Mouse Model

scholarly journals The TLR3 Agonist Poly Inosinic:Cytidylic Acid Significantly Augments the Therapeutic Activity of an Anti-CD7 Immunotoxin for Human T-cell Leukaemia

Biomedicines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 13 ◽  
Author(s):  
David J. Flavell ◽  
Suzanne E. Holmes ◽  
Sarah L Warnes ◽  
Sopsamorn U. Flavell
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Nk Cells ◽  
Scid Mouse ◽  
Scid Mice ◽  
Poly I:C ◽  
Cell Leukaemia ◽  
Therapeutic Activity ◽  
Human T Cell ◽  
Scid Mouse Model

We have previously shown that antibody-dependent cellular cytotoxicity (ADCC) cooperates with immunotoxin (IT)-mediated killing of human leukaemia cells in an severe combined immunodeficient (SCID) mouse model of human T-cell acute lymphoblastic leukaemia (SCID-HSB-2 mice), but not in an equivalent non-obese diabetic (NOD)/SCID mouse model. In these earlier studies, we reasoned that diminished ADCC due to the functional deficit in natural killer (NK) cell activity in NOD/SCID mice resulted in a failure of effective perforin/granzyme-mediated cytotoxicity necessary for the delivery of the augmentative effect. Poly-inosinic-cytidylic acid [poly (I:C)] is a synthetic dsRNA toll-like receptor 3 (TLR3) agonist that possesses a number of biological properties that includes the in vivo activation of NK cells. We show here that intravenous (i.v.) injection of SCID mice with [poly (I:C)] results in characteristic time-related changes in serum interleukin 2 (IL-2), IL-12, and interferon γ (INFγ) cytokine levels that are consistent with TLR3 driven activation of SCID mouse NK cells. Concomitantly, there are changes in the expression levels of CD2, CD16/32 (FcγRII/RIII), CD161 (NK1.1), and F4/80 in the bulk splenocyte population. These observed changes correlate with an increase in the in vitro lytic capabilities of putative NK cells from within the splenocyte population of [poly (I:C)] treated SCID mice. We demonstrate that the in vivo activation of NK cells with [poly (I:C)] in SCID mice bearing disseminated human T-cell leukaemia xenografts resulted in a significant improvement in the therapeutic activity exerted by an intact murine monoclonal antibody against human CD7. This was also seen for a saporin-based immunotoxin constructed with the same intact antibody (HB2-SAPORIN), but not with an F(ab’)2 derivative of the same antibody or of an IT constructed with the same F(ab’)2 HB2 antibody derivative. This study further demonstrates the previously reported reinforcing role of ADCC for the therapeutic activity of IT in an SCID mouse model of human T-ALL and the potential to significantly boost this further with [poly (I:C)]. Our study provides the rationale to justify the exploration of the clinical utility of IT based therapeutics in combination with TLR3 agonists, such as [poly (I:C)], for the treatment of haematological, and possibly other, malignancies.

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