scholarly journals Too Much of a Good Thing: High T Cell Count Can Kill Newborns

2019 ◽  
Vol 2 (2) ◽  
pp. 15-16
Author(s):  
Angelina Bustos ◽  
Lai Xu ◽  
Garett Dunsmore ◽  
Shokrollah Elahi
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Cd8 T Cells ◽  
Adaptive Immune Response ◽  
Spleen Cells ◽  
Robust Immune Response ◽  
Adaptive Immune ◽  
Neonatal Immunity ◽  
Low Exposure

Neonates have a weakened immune system that could be due to low exposure to pathogens resulting in low adaptive immunity and/or purposeful immune suppression to protect the weak neonate from a robust immune response. The purpose of this project is to find preliminary data to further investigate why the immune system of neonates are weaker, and to possibly improve neonatal immunity while protecting against a powerful immune response in the future.  Using processed mice spleen cells that were stained for CD4 and CD8 to be subjected to flow cytometry, an increase in the percent of helper CD4 and killer CD8 T cells were observed as the mice aged. This indicates that neonates do have a weaker immune system. Between healthy mice and mice infected with either Bordetella pertussis or Listeria, a decrease in the percent of CD4 and CD8 T cells were found, which could be because not enough time had passed for an adaptive immune response.

Double positive CD4+CD8+ T cells are part of the adaptive immune response against Candida albicans

2019 ◽  
Vol 80 (12) ◽  
pp. 999-1005 ◽  
Author(s):  
Barbara Misme-Aucouturier ◽  
Adel Touahri ◽  
Marjorie Albassier ◽  
Francine Jotereau ◽  
Patrice Le Pape ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Candida Albicans ◽  
Cd8 T Cells ◽  
Adaptive Immune Response ◽  
Double Positive ◽  
Adaptive Immune

scholarly journals Analysis of the Intratumoral Adaptive Immune Response in Well Differentiated and Dedifferentiated Retroperitoneal Liposarcoma

Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
William W. Tseng ◽  
Shruti Malu ◽  
Minying Zhang ◽  
Jieqing Chen ◽  
Geok Choo Sim ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Immune Checkpoint ◽  
Cd4 T Cells ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Retroperitoneal Liposarcoma ◽  
Well Differentiated

Treatment options are limited in well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma. We sought to study the intratumoral adaptive immune response and explore the potential feasibility of immunotherapy in this disease. Tumor-infiltrating lymphocytes (TILs) were isolated from fresh surgical specimens and analyzed by flow cytometry for surface marker expression. Previously reported immune cell aggregates known as tertiary lymphoid structures (TLS) were further characterized by immunohistochemistry. In all fresh tumors, TILs were found. The majority of TILs were CD4 T cells; however cytotoxic CD8 T cells were also seen (average: 20% of CD3 T cells). Among CD8 T cells, 65% expressed the immune checkpoint molecule PD-1. Intratumoral TLS may be sites of antigen presentation as DC-LAMP positive, mature dendritic cells were found juxtaposed next to CD4 T cells. Clinicopathologic correlation, however, demonstrated that presence of TLS was associated with worse recurrence-free survival in WD disease and worse overall survival in DD disease. Our data suggest that an adaptive immune response is present in WD/DD retroperitoneal liposarcoma but may be hindered by TLS, among other possible microenvironmental factors; further investigation is needed. Immunotherapy, including immune checkpoint blockade, should be evaluated as a treatment option in this disease.

scholarly journals Multifaceted influence of pre-mitotic cytotoxicity of primed CD8 T cells on immunity and infection

2018 ◽  
Author(s):  
Durga Bhavani Dandamudi ◽  
David A Blair ◽  
Raquel Duque do Nascimento Arifa ◽  
Juan J Lafaille ◽  
Michael L Dustin ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd8 T Cells ◽  
Secondary Infection ◽  
Granzyme B ◽  
Adaptive Immune Response ◽  
Lymphocytic Choriomeningitis ◽  
Cell Repertoire ◽  
Adaptive Immune ◽  
Window Of Vulnerability

AbstractGranzyme B mRNA is expressed in primed CD8 T cells within 12 hours, but the consequences of this for the immune response are unknown. We observed that substantial portion of the naïve CD8 T cell repertoire expressed granzyme B and became pre-mitotic cytotoxic cells (PMCs) immediately in response toListeria monocytogenesorLymphocytic choriomeningitis virusinfections. The surprising breadth arose from sufficiency of low potency peptide-MHC to induce granzyme B expression in the context of infection. PMCs killed antigen bearing dendritic cells (DCs) in a granzyme B-dependent but largely perforinindependent fashion between 1-2 days post infection. This terminated antigen presentation at 3 days and resulted in reduced clonal expansion. As additional consequences, we highlight that PMCs reduced the burden of DC-borne infectious agents, but also opened a window of vulnerability for secondary infection. Thus, PMCs serve antigen-specific, regulatory and host defence functions, that are innate-like in scale, at the onset of the adaptive immune response.

scholarly journals Chemokines are Underestimated in Preventing the Metastasizing and the Immune Elimination of Ovarian Cancer

2019 ◽  
Author(s):  
Ruurd Torensma ◽  
Petra Zusterzeel
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Adaptive Immune Response ◽  
Inhibitory Response ◽  
T Cell Response ◽  
Activated T Cells ◽  
Adaptive Immune

Nowadays the positive immune involvement in the eradication of tumor cells is assigned to the adaptive immune response. By awakening of in vivo responding T cells that are suppressed by the tumor and prevents immunological cure of the cancer. The adaptive immune response is a complex of different cells and protein molecules. Normally activated T cells are well-ordered by several late occurring inhibitors to contain the response to the unknown invaders and spare the normal cells. The tumor strengthens this inhibitory response to escape from immune elimination. Immunotherapy is to unleash the full capacity of the adaptive immune system by blocking this inhibitor response by monoclonal antibodies but with the potential drawback of autoimmune phenomena. Seen the success of the immunotherapy another feature of the immune system is overlooked. Cytokines and chemokines became in oblivion after their suspected necrosis of the tumor (TNF) did not fulfil their initial hope. When patients seek help for their complaints the ovarian cancer is in most cases already metastasized to the peritoneum and omentum. Here, we show that on the one hand chemokines produced by Th2, CD8 and NK cells inhibit cancer spreading and thus leads to a better operability and thus better survival. On the other hand, chemokine receptors are expressed by the tumor that are a decoy by binding chemokines that normally should attract antigen cross-presenting dendritic cells, which start an adaptive T cell response.

scholarly journals Activated adaptive immune system in dissected bicuspid aortic valve aortas: trigger for dissection?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.H.J Staal ◽  
K.R.G Cortenbach ◽  
M.A.J Gorris ◽  
G.S.C Geuzebroek ◽  
L.J Wisse ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Aortic Valve ◽  
Adaptive Immune Response ◽  
Adaptive Immune System ◽  
Helper T Cells ◽  
Funding Source ◽  
Adaptive Immune ◽  
The Media

Abstract Background/Introduction Bicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV. Despite, indication for preventive surgery is presently only defined by vessel diameter which is poor marker for dissection, as it does not take other processes responsible for the vulnerability of the aorta into account. Purpose Inflammation is not considered a player in BAV aortopathy. We introduce a quantitative immunohistochemistry (IHC) approach to sensitively look at the potential role of both the innate and adaptive immune system in BAV aortopathy. Methods Dilated (n=8), non-dilated (n=14) and dissected (n=4) BAV ascending aortas were collected during surgery or from post-mortem donors. Median time from symptoms to surgery for dissections was just over 4 hours. Tissue was stained with a novel 8-colour IHC technique allowing for simultaneous visualization of 6 markers per slide, completed with DAPI nuclear counter-stain and elastin fiber autofluorescence. One panel focused on the adaptive immune system (identifying B cells and classic dendritic cells type 2 (cDC2s) and phenotyping T cells), and the other on the innate immune system (assessing macrophage polarization and neutrophil extravasation). All cells were identified and comprehensively phenotyped using automated quantitative analysis. Results Aneurysm formation was associated with an organized and consistent increase of lymphocytes in the adventitia. B cell follicles and helper T cell expansion were identified, suggestive of a targeted adaptive immune response (Fig. 1a). Only dissected aortas showed a statistically significant increase of helper T (p=0.3) and cDC2s (p=0.3) in the media, when compared to non-dilated and dilated samples (Fig. 1b). The short time between dissection symptoms and surgery suggests these cells were present before the dissection occurred. Furthermore, aneurysms and dissections are associated with a shift in macrophage phenotype to the more aggressive M1-like subset. In summary, we found that a progression of aggressive immune cells in the adventitia and media was correlated to a progression in disease state; from normal to dilated to dissected. Conclusions Aorta dilatation in patients with BAV is associated with an expansion of B and helper T cells in the adventitial compartment without changes in the media. This result might indicate an antigen-driven adaptive immune response. Only dissections show an increase in helper T cells and cDC2s in the media, together with polarization of macrophages to a more M1-like phenotype. We hypothesize that antigen-specific helper T cells expand in the adventitia, migrate to the media, and then potentiate macrophages which can eventually lead to tissue degeneration. These associations could shine light on the final step in the deterioration of the aorta towards a dissection. Figure 1. Microscopy results Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): TTW-NWO open technology grant (STW-14716), ERC-2014-StG-336454-CoNQUeST

IMMU-44. AN IMMUNOTHERAPEUTIC VACCINE COMPOSED OF IRRADIATED WHOLE TUMOR CELLS PULSED WITH MANNAN-BAM, TLR LIGANDS AND ANTI-CD40 ANTIBODY INDUCES POTENT IMMUNE RESPONSE IN PRECLINICAL GBM ANIMAL MODEL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi102-vi102
Author(s):  
Herui Wang ◽  
Rogelio Medina ◽  
Juan Ye ◽  
Pashayar Lookian ◽  
Ondrej Uher ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Cells ◽  
T Lymphocyte ◽  
Cd8 T Cells ◽  
Therapeutic Efficacy ◽  
Poly I:C ◽  
Control Group ◽  
Complete Regression ◽  
Adaptive Immune

Abstract Despite numerous therapeutic advances, the treatment of glioblastoma multiforme (GBM) remains a challenge, with current 5-year survival rates estimated at 4%. Multiple characteristic elements of GBM contribute to its treatment-resistance, including its low immunogenicity and its highly immunosuppressive microenvironment that can effectively disarm adaptive immune responses. Hence, therapeutic strategies that aim to boost T-lymphocyte mediated responses against GBM are of great therapeutic value. Herein, we present a therapeutic vaccination strategy that promotes the phagocytosis of tumor cells, enhances tumor antigen presentation, and induces a tumor-specific adaptive immune response. This strategy consists of vaccinations with irradiated whole tumor cells (rWTC) pulsed with phagocytic agonists (Mannan-BAM), TLR ligands [LTA, Poly (I:C), and R-848], and anti-CD40 antibody (collectively abbreviated as rWTC-MBTA). We evaluated the therapeutic efficacy of rWTC-MBTA strategy in a mouse syngeneic GL261 orthotopic GBM tumor model. rWTC-MBTA or vehicle control were administered subcutaneously over the right foreleg three days after intracranial injection of GL261 cells. Complete regression (CR) of intracranial tumors was achieved in 70% (7/10) of rWTC-MBTA treated animals while none survived in the control group. Immunophenotyping analyses of peripheral lymph nodes and brain tumors of rWTC-MBTA treated mice demonstrated: (1) increased mature dendritic cells and MHC II+ monocytes; (2) increased effector (CD62L-CD44+) CD4-T and CD8-T cells; (3) increased cytotoxic IFNγ-, TNFα-, and granzyme B-secreting CD4-T and CD8-T cells. Of note, the therapeutic efficacy of rWTC-MBTA disappeared in CD4-T and/or CD8-T lymphocyte depleted mice. Three mice that achieved CR were rechallenged with 50k GL261 cells intracranially 14 months after the last rWTC-MBTA treatment and all rechallenged animals resisted GL261 tumor development, confirming the establishment of long-term immunological memory against GL261 tumor cells. Collectively, our study demonstrated that rWTC-MBTA strategy can effectively activate antigen presenting cells and induce more favorable T-cell signatures in the GBM tumors.

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