Th1/Th2 cytokine profiles and their relationship to clinical features in patients following nonmyeloablative allogeneic stem cell transplantation

Guo, Hongwei; Qiao, Zhongdong; Zhu, Lihong; Wang, Hongwei; Su, Liping; Lu, Yong; Yuee, Cui; Jiang, Bo; Zhu, Q J; Xu, Lianrong

doi:10.1002/ajh.10443

Cited by 18 publications

(8 citation statements)

References 24 publications

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“…↓CD4+IFN+ and ↓CD8+IFN+ as indicators of relapse ↑CD4+IFN+ and ↑CD8+IFN+ as indicators of aGVHD [12] SOT Therapeutic immunodefficiency is dependant on drug dose and duration of treatment [27] CMV-CD8+ as predictors of CMV viremia, disease severity and relapse [28] ↓CMV-CD8+CD69+IFN+ as predictor of CMV infection in SOT patients (kidney and liver) [29] 1B), denying the assessment of intracellular colocalization of multiple cytokines. However, this issue can be easily avoided in future research by using customized antibodies instead.…”

Section: Nstmentioning

confidence: 99%

“…ICS proved to be a very versatile and reliable method and is now widely used in research for the study of vaccines, antigen response, autoimmune disorders, cancer, etc. (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) The aim of this study was to investigate the variability of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) synthetic capacity of ex-vivo stimulated CD4+/CD8+ lymphocyte subpopulations in healthy subjects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Variability of ex-vivo stimulated T-cells secretory profile in healthy subjects

Manescu

Manu

Șerban

et al. 2020

Revista Romana De Medicina De Laborator

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Peripheral blood lymphocytes (PBL) are able to synthesize various cytokines that play key roles in the immune response and intercellular signaling. Since alterations in cytokine production and/or activity occur in many pathological processes, the study of cytokine synthetic capacity of PBL is a valuable tool for assessing the immune profile. In this paper, we aimed to investigate the variability of interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) synthetic capacity of CD4+/CD8+ T-cells stimulated ex-vivo in healthy subjects, by means of a commercial intracellular cytokine staining (ICS) protocol. Peripheral blood mononuclear cells were isolated from 16 healthy subjects by Ficoll gradient centrifugation and activated ex-vivo with PMA/Ionomycin/Brefeldin-A for 4 hours. Activated PBL were surface-stained for CD3/CD4/CD8, fixed and permeabilized. ICS was performed using anti-human IL-2/TNF-α/IFN-γ and samples were analyzed on a BD-FACSAria-III flow cytometer. We recorded high post-isolation and post-activation mean viabilities: 82.1% and 82.4% respectively, p=0.84. Both CD4+/CD8+ subpopulations were found to partially produce each of the three cytokines, but in different proportions. On average, a significantly greater percentage of CD4+ cells was shown to produce IL-2 and TNF-α, compared with CD8+ cells (61.5%+/-5.8 vs. 25%+/-5.6 and 26.9%+/-11 vs. 7.5%+/-3.3 respectively, p---lt---0.0001 for both). Contrarily, IFN-γ was produced by a higher proportion of CD8+ cells (8.4%+/-3.9 vs. 6.8%+/-3.2, p=0.01). These results show that the employed ICS protocol elicits a satisfactory and consistent cytokine response from PBL of healthy subjects. The collected data may be used to outline a preliminary reference range for future studies on both healthy/pathological subjects.

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Section: Nstmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Variability of ex-vivo stimulated T-cells secretory profile in healthy subjects

Manescu

Manu

Șerban

et al. 2020

Revista Romana De Medicina De Laborator

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“…Cytokine polarization is a relative definition that reflects the relative ratio of type 1 cytokines over type 2 cytokines [29]. Th1 cytokines are the main mediators in GVHD production.…”

Section: Roc Curvementioning

confidence: 99%

Interferon Gamma/IL10 Ratio Production in Response to Host Antigens may Predict Acute Graft Versus Host Disease after Allogeneic Stem Cell Transplantation from a Sibling

Kamel¹,

El-Sharkawy²,

El-Fattah³

et al. 2013

J Leuk

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Background: Graft versus host disease (GVHD) continues to be the main concern of transplanters. Cytokines' contribution to its pathogenesis has been widely addressed in the literature. Previous studies have mainly evaluated the cytokine's level after the actual occurrence of GVHD. In this work, we investigated the possibility of predicting the occurrence of acute GVHD through an experimental setup to mimic the response of the immune cells of the graft to the host antigens expressed by interferon gamma (IFNγ) and interleukin 10 (IL10) production. Methods: The study included 45 patients receiving allogeneic HSCT from an identical sibling. An aliquot from the graft prior to infusion was used for in vitro culture for 3 days with patients' mitomycin treated mononuclear cells. IFNγ and IL10 were measured in culture supernatant using microbead array technology. Results: Acute GVHD was encountered in 14 cases. IFNγ was detectable in the culture supernatant of 9/14 (64.3%) cases with GVHD at a level of 6.2-19.000 with a median of 159.3 pg/ml versus 3/31 (9.6%) cases without GVHD at a level of 1.1, 8.1 and 80.01 pg/ml (p<0.001). IL10 was detectable in the culture supernatant of 7/14 (50%) cases with GVHD at a level of 9.5-858.5 with a median of 128 pg/ml versus 6/31 (19.3%) cases without GVHD at a level of 14.0-359.0 with a median of 45.39 pg/ml (p<0.05). At a cutoff of 1.13, IFNγ/IL10 ratio could predict GVHD with a sensitivity of 85.7%, specificity of 83.3% and a total accuracy of 84.6%. Conclusion: In vitro cytokine production by graft immune cells in response to host antigens is extremely variable. IFNγ production apparently reflects potential development of acute GVHD while IL10 production is apparently protective. When both are produced the IFNγ/IL10 ratio is more informative than either alone.

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“…Such disparate genotype‐induced immune response profiles, if present within human patient populations, would be expected to have significant effects on both graft survival and responses to immunosuppression and tolerance induction therapies. Human patients with different predetermined IR biases have been described previously in various contexts such as Helicobacter pylori infection [27], T‐cell lymphomas [28], allogeneic stem cell transplantation [29, 30], HIV‐1 infection [31] and asthma [32]. In these clinical conditions, patient groups predisposed toward different IR biases often responded differently to the same therapeutic or prophylactic interventions, requiring treatments to be tailored to individual IR characteristics.…”

Section: Discussionmentioning

confidence: 99%