Effect of sesquiterpene lactones on the expression of the activation marker CD69 and of IL-2 in T-lymphocytes in whole blood

2003 ◽  
Vol 65 (9) ◽  
pp. 1551-1563 ◽  
Author(s):  
Matjaz Humar ◽  
Alfonso J Garcı́a-Piñeres ◽  
Vı́ctor Castro ◽  
Irmgard Merfort
2017 ◽  
Vol 6 (8) ◽  
pp. 758-765 ◽  
Author(s):  
Borros Arneth

Background The origin of autoimmune disease type 1 diabetes is still unknown. Aim This study assessed the activation of CD4+ and CD8+ T-lymphocytes by human insulin and human glutamate decarboxylase (GAD) in patients with type 1 or type 2 diabetes mellitus (DM) and healthy volunteers. Materials and methods The expression of CD69, a marker of T-lymphocyte activity, was determined in whole blood samples by flow cytometry after 12 h of incubation with or without insulin or GAD. The analysis included samples from 12 type 1 DM patients, 14 type 2 DM patients and 12 healthy volunteers. Results Significant increases in the number of activated CD4+ and CD8+ T-lymphocytes following pre-incubation of whole blood samples with human insulin or GAD were observed in samples from patients with type 1 DM, whereas no activation of these cells was detected in samples from either type 2 DM patients or healthy subjects. Discussion These results indicated that latent pre-activation of CD4+ and CD8+ T-lymphocytes in response to insulin or GAD epitopes occurred in type 1 DM patients. Conclusion These findings suggest that pre-immunization against insulin and/or GAD might be associated with the development of type 1 DM. Alternatively, these results might reflect a non-specific, bystander autoimmune response.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4307-4307
Author(s):  
Noriega Concepcion Victor ◽  
Gayoso Jorge ◽  
David Serrano ◽  
Rodriguez Macias Gabriela ◽  
Pascual Balsalobre ◽  
...  

Abstract Abstract 4307 Introduction Complications after Allogenic Stem Cell Transplantation (Allo-SCT) are influenced by the immunological fenomena associated to the alloreactivity/allotolerance between donor and recepient. In this context, the usefulness of chimerism quantification in T lymphocytes for the prediction of complications after Allo-SCT is well known. However, to our knowledge, there is no information on the utility of chimerism analysis in activated lymphocytes (CD25+). Objective To stablish an asociation betwen the more common complications post Allo-Tph (aGVHD, cGVHD, relapse, reject), and the chimerism dynamics in CD25+ activated lymphocytes in the early period post-transplantation, trying to predict the patients with more risk of suffering from this complications. Materials and Methods The study included 38 Allo-SCT (17 NMA, 21 MA; 7 Haploidentical, 13 non-related donor, 18 identical donor; 7 UCB, 5 BM, 26 PB). Chimerism analysis was performed every 2 weeks until complete chimerism (CC) was achieved, and every 3 months thereafter. Follow up was censored when patients received DLI or 2nd Allo-SCT.Chimerism quantification was performed by microsatellite PCR (STR-PCR; AmpFlSTR SGM Plus; Applied Biosystems) on DNA obtained from peripheral blood and purified cell lineages (95% putity) by immunomagnetic technology (Miltenyi Biotec). Results Table 1 shows the results at day +30 for T and activated lymphocytes (CD3+ and CD25+) allocating patients in two groups depending on the relative percentage of recipient cells (% rec) in both cell lineages. 20 patients were in CC in CD25+, maintening this CC during the study. 18 patients were found in MC in CD25+ (18/38 MC). 1/18 was in CC in CD3+ TL, and 10/18 were in CC in whole blood. 17/18 were in MC both in CD3+ and CD25+ lymphocytes, Although no statistical significance is achieved due to the reduced sample size, patients in the first group (% rec higher in activated that in T lymphocytes) tend to achieve CC later and to show higher risk of developing complications such as acute and chronic GVHD, relapse or rejection. Conclusions A higher incidence of complications post Allo-SCT (aGVHD, cGVHD, relapse, rejection) in patients with % of recipient in CD25+> % recipient in CD3 at day 30. Chimerism analysis in activated lymphocytes (CD25+) is of great utility after Allo-SCT since it allows beter prediction of complications than standard follow up of whole blood or T lymphocytes. Disclosures: No relevant conflicts of interest to declare.


2003 ◽  
Vol 35 (4) ◽  
pp. 582-588 ◽  
Author(s):  
KATHERINE J. GREEN ◽  
DAVID G. ROWBOTTOM ◽  
LAUREL T. MACKINNON

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65413 ◽  
Author(s):  
Katarina Radulovic ◽  
Valerio Rossini ◽  
Calin Manta ◽  
Karlheinz Holzmann ◽  
Hans A. Kestler ◽  
...  

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 756-765 ◽  
Author(s):  
S Siena ◽  
DA Lappi ◽  
M Bregni ◽  
A Formosa ◽  
S Villa ◽  
...  

Abstract The authors conjugated, by a disulphide bond, the antihuman T- lymphocyte (CD5) monoclonal antibody (MoAb) OKT1 to the saporin-6 (SAP) ribosome-inactivating protein of the plant Saponaria officinalis. The resulting OKT1-SAP immunotoxin bound to CD5-expressing target cells and under standard culture conditions specifically suppressed mitogen- induced-T-lymphocyte DNA and protein synthesis in a dose-related manner. T-lymphocyte killing was achieved by five-minute exposure of the target cells to OKT1-SAP. The concentration inhibiting 50% (IC50) of T-lymphocyte DNA synthesis was 0.32 nmol/L. The potency of OKT1-SAP was moderately enhanced by amantadine (IC50 0.08 nmol/L) but not by ammonium chloride or chloroquine. Whole blood components did not interfere with the efficacy of OKT1-SAP, as in vitro treatment of fresh whole blood resulted in effective elimination of clonable peripheral blood T-lymphocytes assessed by a limiting dilution assay. Because these characteristics of T-lymphocyte killing by OKT1-SAP (ie, rapidity of action, potency also without potentiators) and lack of inhibition by whole blood components may be relevant for the use of an immunotoxin as a therapeutic agent in humans, the authors evaluated the stability in vivo and the circulatory clearance of OKT1-SAP in cynomolgus monkeys. Following a single intravenous (IV) injection of nontoxic dosages (0.16 to 1.3 mg/kg), an initial rapid decline (t1/2 alpha = 1.0 to 4.1 hours) was followed by a long-lasting slower decrease (t1/2 beta = 11.6 to 20.6 hours) of OKT1-SAP plasma concentrations as detected by double- antibody solid phase enzyme-linked immunosorbent assay (ELISA) assay. Not only did OKT1-SAP remain intact immunologically but it also retained its biological activity, as measured by the ability of plasma samples from monkeys given immunotoxin to inhibit DNA synthesis in human T-lymphocytes. Taken together the findings presented in this article indicate the feasibility of using OKT1-SAP as a therapeutic tool and provide information that will facilitate the rational use of immunotoxins as a treatment modality in humans.


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