1097 Role of PD-L1 in In-vitro Interaction Between T-cells and Ovarian Tumour Cells

2012 ◽  
Vol 48 ◽  
pp. S264
Author(s):  
J. Chatterjee ◽  
N. Haslinda Abdul Aziz ◽  
C. Maine ◽  
C. Hayford ◽  
L. Whilding ◽  
...  
1992 ◽  
Vol 176 (2) ◽  
pp. 575-579 ◽  
Author(s):  
W T Lee ◽  
E S Vitetta

We have used staphylococcal enterotoxin B (SEB) to study the role of naive and memory T cells in the induction of peripheral tolerance. After administration of SEB to mice, the numbers of naive and memory T cells increase, as does the proportion of memory T cells, which are unresponsive to further stimulation with SEB in vitro. In addition, memory T cells generated in response to conventional antigen, which proliferate and provide help to B cells in the presence of the conventional antigen, fail to respond to superantigen. Hence, memory T cells, in general, are anergized by SEB. These results suggest that SEB-induced activation and anergy reflect the combined responses of naive and memory T cells. The differential activation vs. anergy of naive and memory T cells by superantigen may be related to cytokine production and may play an important role in the etiology of autoimmune diseases or immunodeficiency diseases such as acquired immune deficiency syndrome.


2006 ◽  
Vol 74 (7) ◽  
pp. 3817-3824 ◽  
Author(s):  
Karen L. Wozniak ◽  
Jatin M. Vyas ◽  
Stuart M. Levitz

ABSTRACT Dendritic cells (DC) have been shown to phagocytose and kill Cryptococcus neoformans in vitro and are believed to be important for inducing protective immunity against this organism. Exposure to C. neoformans occurs mainly by inhalation, and in this study we examined the in vivo interactions of C. neoformans with DC in the lung. Fluorescently labeled live C. neoformans and heat-killed C. neoformans were administered intranasally to C57BL/6 mice. At specific times postinoculation, mice were sacrificed, and lungs were removed. Single-cell suspensions of lung cells were prepared, stained, and analyzed by microscopy and flow cytometry. Within 2 h postinoculation, fluorescently labeled C. neoformans had been internalized by DC, macrophages, and neutrophils in the mouse lung. Additionally, lung DC from mice infected for 7 days showed increased expression of the maturation markers CD80, CD86, and major histocompatibility complex class II. Finally, ex vivo incubation of lung DC from infected mice with Cryptococcus-specific T cells resulted in increased interleukin-2 production compared to the production by DC from naïve mice, suggesting that there was antigen-specific T-cell activation. This study demonstrated that DC in the lung are capable of phagocytosing Cryptococcus in vivo and presenting antigen to C. neoformans-specific T cells ex vivo, suggesting that these cells have roles in innate and adaptive pulmonary defenses against cryptococcosis.


Cytokine ◽  
2018 ◽  
Vol 102 ◽  
pp. 107-116 ◽  
Author(s):  
Anna Bieńkowska ◽  
Ewelina Kiernozek ◽  
Ewa Kozlowska ◽  
Łukasz Bugajski ◽  
Nadzieja Drela

Author(s):  
Mohammad H. Rashid ◽  
Thaiz F. Borin ◽  
Roxan Ara ◽  
Raziye Piranlioglu ◽  
Bhagelu R. Achyut ◽  
...  

AbstractMyeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME), and our perception regarding the role of MDSCs in tumor promotion is attaining extra layer of intricacy in every study. In conjunction with MDSC’s immunosuppressive and anti-tumor immunity, they candidly facilitate tumor growth, differentiation, and metastasis in several ways that yet to be explored. Alike any other cell types, MDSCs also release a tremendous amount of exosomes or nanovesicles of endosomal origin and partake in intercellular communications by dispatching biological macromolecules. There has not been any experimental study done to characterize the role of MDSCs derived exosomes (MDSC exo) in the modulation of TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant amount of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those are in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating the mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that immunosuppressive and tumor-promoting functions of MDSC are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.


2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Abdallah Sassine Geara ◽  
Mario R. Castellanos ◽  
Claude Bassil ◽  
Georgia Schuller-Levis ◽  
Eunkue Park ◽  
...  

Parathyroid hormone (PTH) function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide) in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells). The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human), at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.


2005 ◽  
Vol 18 (2) ◽  
pp. 269-276 ◽  
Author(s):  
F. Martini ◽  
C. Agrati ◽  
G. D'Offizi ◽  
F. Poccia

Alterations in NK cell numbers and function have been repeatedly shown during HIV infection. In this study, NK cell number and MHC class I expression on CD4+ T cells were studied in HIV patients at different stages of disease progression. An increased expression of HLA-E was seen on CD4+ T cells. In parallel, a reduced number of CD94+ NK cells was observed in advanced disease stages. Moreover, a decline in CD94 expression on NK cells was observed at the HIV replication peak in patients undergoing antiretroviral treatment interruption, suggesting a role of viral replication on NK cells alterations. In vitro HIV infection induced a rapid down-regulation of HLA-A,B,C expression, paralleled by an increased expression of HLA-E surface molecules, the formal ligands of CD94 NK receptors. HIV-infected HLA-E expressing cells were able to inhibit NK cell cytotoxicity through HLA-E expression, since cytotoxicity was restored by antibody masking experiments. These data indicate that the CD94/HLA-E interaction may contribute to NK cell dysfunction in HIV infection, suggesting a role of HIV replication in this process.


2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Paresa Taghavie-Moghadam ◽  
Matthew Butcher ◽  
Mark Kaplan ◽  
Jerry Nadler ◽  
Elena Galkina

T helper 1 (Th1) cells constitute the majority of plaque infiltrating IFNγ+ T cells and play a pro-atherogenic role. Th1 cells are induced via IFNγ-dependent activation of T-box expressed in T cells (Tbet) and/or IL-12-dependent activation of signal transducer and activator of transcription 4 (Stat4). While the role of Tbet in atherosclerosis is established, the impact of the IL-12/Stat4-dependent pathway is not well defined. To address the role of Stat4 in atherosclerosis, we bred Stat4-deficient mice with Apolipoprotein E-deficient mice to generate Stat4-/-Apoe-/- mice. Deficiency of Stat4 resulted in approximately a 70% reduction in the plaque burden for 34 week old Stat4-/-Apoe-/- mice fed a chow diet and in 12 week old Stat4-/-Apoe-/- mice fed a western diet there was approximately a 40% reduction in plaque burden, both compared with diet matched Apoe-/- controls females (p<0.001). To assess the effect of Stat4 on Th1 and Treg cell differentiation, we performed an in vitro polarization assay. Deficiency of Stat4 reduced differentiation of IFNγ+ Th1 cells in Th1 conditions, but supported the induction of Tregs in Treg polarizing conditions, confirming the importance of Stat4 in regulating the Th1/Treg balance. In contrast to the in vitro results, we found no difference in the expression of both IFNγ and Foxp3 amongst Stat4-/-Apoe-/- and Apoe-/- lymph nodes and splenic CD4+ T cells; suggesting that additional cytokines in vivo may induce IFNγ+Th1 and inhibit Treg differentiation. Stat4 deficiency also resulted in increased splenic B cell numbers and a slight increase in B1a dependent T15/E06 mRNA expression. Stat4 is a powerful regulator of chemokine expression within peripheral tissues. Adoptively transferred Apoe-/- B cells and CD11b+ cells migrated more efficiently into Stat4-/-Apoe-/- aortas compared to Apoe-/- recipients. However, percentages of macrophages, as determined by CD11b+CD68+ were reduced within the spleens and aortas of Stat4-/-Apoe-/- mice as compared to Apoe-/- controls at steady state conditions. In conclusion, Stat4 deficiency results in reduced atherosclerosis via the modulation of B cell function and aortic leukocyte content.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Zhifang Chen ◽  
Yuejie Zhu ◽  
Rong Du ◽  
Nannan Pang ◽  
Fengbo Zhang ◽  
...  

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P<0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P<0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r=0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P<0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r=‐0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P<0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masaru Shimizu ◽  
Yuya Kondo ◽  
Reona Tanimura ◽  
Kotona Furuyama ◽  
Masahiro Yokosawa ◽  
...  

AbstractT-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-betfl/fl (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA.


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