Enhanced propensity of T lymphocytes in patients with systemic lupus erythematosus to apoptosis in the presence of tumour necrosis factor alpha

Habib, HM; Taher, T. E. I.; Isenberg, David; Mageed, RA

doi:10.1080/03009740802409496

Cited by 19 publications

(14 citation statements)

References 50 publications

(46 reference statements)

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“…Consistent with a previous study, preliminary results demonstrated that the Fas gene was markedly expressed in SKOV3 cells following co-transfection with Ad5-hTERT-GAL4VP2 and Ad5-G5E4T-Fas, whereas Fas expression in the control lung fibroblast cell line HELF was not altered following transfection, indicating the efficient targeted expression of Fas in human ovarian cancer cells using the TSTA system (7). As a subgroup of T cells, γδ T cells are able to directly bind to antigens, including polypeptides and lipids, owing to the rich surface expression of FasL, and thus can effectively target Fas-expressing tumor cells, initiating the Fas/FasL apoptotic pathway (25)(26)(27)(28)(29). Preliminary results confirmed the strong killing activity of γδ T cells against adenovirus-mediated Fas-expressing SKOV3 cells (7).…”

Section: Discussionmentioning

confidence: 68%

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma

Zeng

Lin

et al. 2017

Oncol Lett

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Abstract. The present study aimed to investigate the therapeutic effect and safety of targeted use of Fas-expressing adenoviruses combined with γδ T cell-mediated killing to treat human ovarian cancer xenografts in BALB/c mice. Shuttle plasmids containing control elements of human telomerase reverse transcriptase promoter and two-step transcriptional amplification system were constructed and packaged into adenovirus-5 vectors to generate expression of an exogenous Fas gene. A mouse xenograft model of human ovarian carcinoma was constructed. A total of 35 BALB/c mice were randomly divided into five groups, which were injected with PBS, γδ T cells, Fas-expressing adenoviruses, taxol, or Fas-expressing adenovirus and γδ T cells. The weight and volume of tumors in mice in each group was monitored. Tissue sections of the various tissues of mice in the Fas-expressing adenovirus and γδ T cells group was compared with those in the PBS group to evaluate the safety of Fas-expressing adenovirus and γδ T cells in the treatment of human ovarian cancer xenograft tumors. The results of the present study indicated that mice in all treatment groups were alive at the end of the treatment course. Tumor weight and volume was the highest in the PBS group, followed successively by the adenovirus group, the γδ T cell group, the adenovirus and γδ T cell group, and the taxol group. The weight and volume inhibition rate in adenovirus and γδ T cell group were significantly higher compared with in the PBS group (P<0.05). Pathological observation of tissue samples revealed that none of vital organs in the adenovirus and γδ T cell group developed any evident morphological changes during treatment, when compared with healthy controls. In conclusion, the combined therapy with Fas-expressing adenoviruses and γδ T cells is efficient and safe for the treatment of mouse human ovarian carcinoma xenografts.

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Section: Discussionmentioning

confidence: 68%

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma

Zeng

Lin

et al. 2017

Oncol Lett

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“…The level of apoptosis tested by flow cytometry may not necessarily reflect the real leukocyte physiologic function in vivo . Similar protocols are used to detect cell apoptosis [29,32,33]. Second, this is a cross-sectional observational study.…”

Section: Discussionmentioning

confidence: 99%

The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus

Cheng

Chen

et al. 2013

J Transl Med

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BackgroundBoth apoptosis and autoantibodies are important factors associated with disease activity in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of SLE.MethodsLeukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 23 patients with SLE. Leukocyte apoptosis was also evaluated in nine patients with Sjogren’s syndrome (SJS) and in 20 volunteer subjects. Titers of common autoantibodies and the disease activity index (SLEDAI-2 k) of the SLE patients were also determined.ResultsExcept for annexin V and APO 2.7 of monocytes and late apoptosis (annexin V + 7-ADD) of lymphocytes, apoptosis in the total and in subsets of leukocytes were significantly higher in SLE patients than in controls (all p < 0.05, post hoc analysis). The mean percentage of late apoptosis of leukocytes (annexin V + 7-AAD) positively correlated with levels of anti-Ro52/60 (r = 0.513, p < 0.01), anti-La (r = 0.439, p = 0.04), and anti-Mi-2 (r = 0.492, p = 0.02), and inversely correlated with both C3 and C4 levels, although not statistically significant. The percentage of APO2.7 of CD19+ cells positively correlated with SLEDAI-2 K score (p = 0.01).ConclusionsLeukocyte apoptosis is significantly higher in patients with SLE and correlates well with the levels of several autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates with the disease activity of SLE.

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“…Thus the exaggerated T-cell responses characteristic of SLE could be attributed to CTLA-4 dysfunction. Although CTLA-4 can induce T-cell apoptosis [38] which might therefore be impaired in lupus due to CTLA-4 dysfunction, in fact lupus T cells display an increased rate of apoptosis compared with healthy T-cells [39][40][41][42]. It remains to be determined whether mechanisms independent of CLTA-4 attempt to delete autoreactive T cells through increased apoptosis or their survival is impaired due to prolonged stimulation.…”

Section: Discussionmentioning

confidence: 99%

Abnormal CTLA‐4 function in T cells from patients with systemic lupus erythematosus

et al. 2010

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CTLA‐4 is a critical gatekeeper of T‐cell activation and immunological tolerance and has been implicated in patients with a variety of autoimmune diseases through genetic association. Since T cells from patients with the autoimmune disease systemic lupus erythematosus (SLE) display a characteristic hyperactive phenotype, we investigated the function of CTLA‐4 in SLE. Our results reveal increased CTLA‐4 expression in FOXP3− responder T cells from patients with SLE compared with other autoimmune rheumatic diseases and healthy controls. However, CTLA‐4 was unable to regulate T‐cell proliferation, lipid microdomain formation and phosphorylation of TCR‐ζ following CD3/CD28 co‐stimulation, in contrast to healthy T cells. Although lupus T cells responded in vitro to CD3/CD28 co‐stimulation, there was no parallel increase in CTLA‐4 expression, which would normally provide a break on T‐cell proliferation. These defects were associated with exclusion of CTLA‐4 from lipid microdomains providing an anatomical basis for its loss of function. Collectively our data identify CTLA‐4 dysfunction as a potential cause for abnormal T‐cell activation in patients with SLE, which could be targeted for therapy.

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Enhanced propensity of T lymphocytes in patients with systemic lupus erythematosus to apoptosis in the presence of tumour necrosis factor alpha

Cited by 19 publications

References 50 publications

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma

Therapeutic effect of targeted Fas-expressing adenoviruses method combining γδ T cells in a mouse model of human ovarian carcinoma

The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus

Abnormal CTLA‐4 function in T cells from patients with systemic lupus erythematosus

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