097 Tissue-resident memory T cells in psoriasis recurrence
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Epidermis (zoology)
Interleukin-7 receptor
In this report we describe a system for the generation of functional, class I MHC-restricted, T-T hybridomas. The BW5147 cell line was transfected with the CD8 gene. BW5147 transfectants were obtained that stably expressed CD8 and this expression was maintained after somatic cell hybridization with activated T lymphocytes. To determine whether the stable expression of CD8 would facilitate the generation of class I MHC-specific T-T hybridomas, the transfected cells were fused with alloreactive T cells and the resultant hybrids were screened for their ability to produce lymphokines in response to antigenic stimulation. Somatic cell hybridizations with BW5147-CD8 transfectants give rise to a much higher frequency of class I MHC-specific T-T hybridomas relative to parallel fusions with BW5147. To determine whether the BW5147-CD8 transfectants would also support the generation of Ag-specific, class I MHC-restricted T-T hybridomas, they were fused with OVA-specific CTL. Several T-T hybrid clones were identified that produced lymphokines after stimulation with a transfected APC that was synthesizing OVA, or with a tryptic digest of OVA in the presence of syngeneic APC. The stimulation by Ag was MHC-restricted and mapped to the Kb molecule. An anti-CD8 mAb inhibited the stimulation of these hybridomas by Ag plus APC, whereas their stimulation by mitogen was unaffected. Cytolytic activity was not detected when several of the OVA-specific or alloreactive hybridomas were tested for their ability to kill target cells bearing the appropriate Ag. These results demonstrate that the BW5147-CD8 transfectants allow the generation of class I MHC-restricted T-T hybridomas. The potential utility of this system is discussed.
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To explore the role of IL-22 on the recovery and function of thymus from graft-versus host disease (GVHD) mice after allogeneic bone marrow transplantation (allo-BMT).GVHD model was established by using of recipient male BALB/c and donor male C57BL/6 mice(6-8 W) respectively. The mice were divided into normal group, GVHD with IL-22 group (BS+IL-22) and without IL-22 group (BS+PBS). Numbers of thymus cells were detected at different time points. The ratio of T cell subsets from thymus was observed by flow cytometry. Percentages of IFN-γ-producing and IL-17-producing CD4+ T or CD8+ T cells were detected.The total number of thymus cells in BS+IL-22 mice [(14.6±5.1)×10⁴] was significantly higher than that in BS+PBS mice [(6.2±2.9)×10⁴] at 14 days after allo-BMT. Thymus cells in BS+IL-22 mice expanded continuously and reached at the level of normal mice, which were still higher than that in BS+PBS group. Although there was no impact on the ratio of mature CD4+ and CD8+ T cell from thymus, the percentage of immature CD4+CD8+ T cell increased obviously in mice treated with IL-22. Percentages of IFN-γ+CD4+ T cell [Th1:(2.42±0.75)%] and IFN-γ+CD8+ T cell [Tc1:(5.44±0.47)%] were up-regulated by IL-22 treatment, whereas no changes were detected in IL-17+CD4+ T cell (Th17) and IL-17+CD8+ T cell (Tc17).IL-22 accelerates the progress of thymus recovery, and increases the IFN-γ-producing ability of thymus CD4+ and CD8+ T cells from GVHD mice.
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Objective To Investigate whether the PDEs activities is abnormal or not in psoriasis patients by detecting the PDEs activities of both psoriasis patients and healthy controls, and explore the potential role of PDEs activities changes in the pathogenesis of psoriasis. Methods PDEs activities were detected by using high performance liquid chromatography(HPLC) in 50 patients with psoriasis and 60 healthy controls. Results The PDEs activities is 10.40%±3.54% in psoriasis patients,and 8.60%±2.25% in the healthy controls. The PDEs activities in patients with psoriasis is significant higher than that in the controls (P0.05). Conclusions The PDEs activities may be a risk factor for psoriasis.
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Background. The in vivo effects of immunosuppressants on T cells are classically determined using animal models of organ transplantation. These methods are technically difficult and time consuming. A simple in vivo method is needed for screening new immunosuppressants. Methods. Donor mouse spleen cells were labeled with a fluorescent dye, carboxy-fluorescein diacetate succinimidyl ester (CFSE), and then injected into the blood of recipient severe combined immunodeficiency mice. Three days after the injection, spleen cells of the recipient mice were isolated and the proliferating alloreactive T cells were analyzed by flow cytometry. Results. In control recipient mice, 50% of the T cells were proliferating, consisting of both CD4+ and CD8+ T cells. In cyclosporine- or FK506-treated mice, T-cell proliferation was suppressed in the CD4 subset but not in the CD8 subset. On the contrary, T-cell proliferation was significantly reduced in the CD8 subset but not in the CD4 subset in recipient mice treated with rapamycin. Conclusion. The present mouse model using carboxy-fluorescein diacetate succinimidyl ester labeling is simple and fast. It is useful for screening new immunosuppressants and for examining the effect on T-cell subsets.
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【Objectives】 To test the expression levels of soluble CD147(sCD147) in plasma of psoriasis vulgaris(PV) patients and normal controls. Describe disease severity of PV with psoriasis lesion degree score(PASI) and analyze the correlation between the expression levels of sCD147 in psoriasis patients and disease severity. To test the expression levels of sCD147 in plasma of different subtypes of psoriasis patients, and study the roles of sCD147 play in the psoriasis classification. 【Methods】 Detect the expression levels of sCD147 in 74 PV patients and 41 normal controls by enzyme-linked immunosorbent assay(ELISA). Analyze the correlation between sCD147 expression levels and PASI score. Detect the expression levels of sCD147 of plasma in 10 patients with psoriasis pustulose(PP), 12 patients with arthritis psoriasis(PsA) and 7 patients with psoriasis erythrodermic(PE). Statistical analyze the difference of sCD147 expression levels in patients with different subtypes of psoriasis. 【Results】 The sCD147 expression levels in plasma of PV patients were significantly higher than those in normal controls(Ctrl)(P 0.01). Statistical analysis showed that there was no correlation between sCD147 expression level and PASI score(r =0.123, P =0.298). There was significant difference of sCD147 expression levels in different subtypes of psoriasis patients(PV PP PsA PE)(P 0.001). 【Conclusion】The expression levels of sCD147 is significantly increased in psoriasis patients. There is statistical significance of sCD147 expression levels in four subtypes of psoriasis. Thus, sCD147 may become a new target for psoriasis drug treatment.
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Objecfive To study T cell subsets distribution in peripheral blood from patients with ankylosing spondylitis(AS)and the role of cell immunity in AS.Methods 30 patients with untreated active phase AS and 30 healthy volunteers were enrolled.The expression of CD4+ and CD8+ T cell subsets were evaluated by flow eytome try.The correlation among T cell subsets and Bath AS function index(BASFI).Bath AS measurement index(BASMI),course of disease,age,ESR,hyper-sensitive C-reactive protein (hs-CRP) were analyzed.Results The level of CD4+ T cell and CD4/CD8+ratio were significantly lower than that of healthy volunteers[(29.24±9.22)% vs.(40.09±6.86) %,(0.96±0.49 ) vs.(1.70±0.67 ),P ＜ 0.01 ],and CD8+ T cell were significantly higher than that of healthy volunteers [(32.91±6.86) % vs.(25.60± 5.97 ) %,P ＜ 0.01 ].The level of CD4+ T cell subsets in peripheral blood of AS patients was negatively correlated with BASMI (r =-0.479,P ＜ 0.01 ),and CD8+ T cell subsets were positively correlated with ESR,hs-CRP,BASFI and BASMI ( r = 0.373,0.430,0.462,0.530,P ＜0.05 ).The ratio of CD4+/CD8+ was negatively correlated with hs-CRP,BASFI and BASMI (r = -0.465,- 0.473,- 0.426,P ＜ 0.05 ).CD4+,CD8+,ratio of CD4/CD8 were not significantly correlated with age and course of disease in patients with AS.Conclusion T cell subsets are significantly abnormal in peripheral blood of patients with AS,and the imbalance degree of T cell is correlated with severity and activity of AS,suggesting that T cell subsets imbalance plays an important role in the pathologensis of AS.
Key words:
Ankylosing spondylitis; T cell subsets; CD4+; CD8+
BASFI
Spondylitis
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Abstract T-cell based immunotherapy represents a promising strategy for chronic viral infections or malignancies. However, its efficacy depends on the infused T cell fitness in vivo. Indeed, T cell exhaustion via the upregulation of PD-1 reflects the maladaptive immune response as the root cause of effector cell failure. To address this issue, we report the development of a novel synthetic fusion cytokine between Granulocyte-macrophage colony stimulating factor (GM-CSF) and Interleukin 7 Fusion Transgene (GIFT7). We show that GIFT7 leads to a hyperagonistic response manifest by increased pSTAT5 and proliferation in CD3+/CD127+ cells. GIFT7 also selectively expand a CD8+ subset from pre-activated T cells with a Central Memory phenotype defined as CD8+CD44+CD62L+CCR7+KLRG-CD27+PD1-, hereafter GIFT7CD8. Adoptive transfer of OTI-derived GIFT7CD8 into OVA+EG7-bearing mice leads to a significant anti-tumor effect. Furthermore, GIFT7CD8 persist long-term whilst IL2-actiaved CD8 T-cells are undetected. We also demonstrate the unique expansive effect of the human ortholog of GIFT7 on peripheral blood mononuclear cells (PBMC) derived from non-human primates (NHP) and humans, in that GIFT7 stimulation of pre-activated PBMC leads to T cell proliferation without exhaustion (Ki67hi and PD1low) in CD4+, CD8+, and CD4-CD8- compartments. This observation supports the use of GIFT7 primed T-cells for chronic viral infections or malignancies where an inadequate T cell response is a common feature.
Interleukin-7 receptor
Memory T cell
Adoptive Cell Transfer
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Abstract The immunology of vertical HIV transmission differs from that of adult infection in that the immune system of the infant is not fully matured, and the factors that influence the functionality of CD8+ T cell responses against HIV in children remain largely undefined. We have investigated CD8+ T cell responses in 65 pediatric subjects with vertically acquired HIV-1 infection. Vigorous, broad, and Ag dose-driven CD8+ T cell responses against HIV Ags were frequently observed in children who were older than 3 years of age and maintained CD4+ T cell counts >400 cells/μl. In contrast, younger age or a CD4+ T cell count <400 cells/μl was associated with poor CD8+ T cell responses and high HIV loads. Furthermore, subjects with a severely depleted and phenotypically altered CD4+ T cell compartment had circulating Gag-specific CD8+ T cells with impaired IFN-γ production. When viral load was not suppressed by antiviral treatment, subjects that fell below the putative age and CD4+ T cell count thresholds had significantly reduced CD8+ T cell responses and significantly higher viral loads. Thus, the data suggest that fully effective HIV-specific CD8+ T cell responses take years to develop despite an abundance of Ag in early life, and responses are further severely impaired, independent of age, in children who have a depleted or skewed CD4+ T cell compartment. The results are discussed in relation to differences between the neonatal and adult immune systems in the ability to respond to HIV infection.
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This chapter contains sections titled: Introduction History of psoriasis Who gets psoriasis? Biology of psoriasis Comorbidities associated with psoriasis Clinical variants of psoriasis Physical symptoms that accompany psoriasis Trigger factors in psoriasis Treatments for psoriasis Measuring quality of life Conclusion References
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