scholarly journals Cross-reactive memory T cells associate with protection against SARS-CoV-2 infection in COVID-19 contacts

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Rhia Kundu ◽  
Janakan Sam Narean ◽  
Lulu Wang ◽  
Joseph Fenn ◽  
Timesh Pillay ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Peripheral Blood Mononuclear ◽  
Protective Function ◽  
Host Protection ◽  
Household Contacts ◽  
Significant Difference ◽  
Membrane Envelope

AbstractCross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.

Reproducibility and Robustness of the Xcellerate III Process for the GMP Manufacture of Xcellerated T Cells™ for Infusion into CLL Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4995-4995
Author(s):  
Lisa Hami ◽  
Cherie Green ◽  
Katharine Miller ◽  
Stewart Craig
Keyword(s):  
T Cells ◽  
Cell Viability ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Total Cell ◽  
Cell Yield ◽  
P Value ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference

Abstract Autologous peripheral blood mononuclear cells (PBMC) cryopreserved from a leukapheresis collection comprise the starting cellular source for the Wave® Bioreactor-based Xcellerate III Process [Hami et al, Bioprocessing Journal2003: 2; 23–32] used for the GMP manufacture of Xcellerated T Cells. For an ongoing clinical trial, n=13 patients have been infused with products manufactured from PBMC cryopreserved and stored in the vapor phase of liquid nitrogen (LN2) for 2–9 days before use in the Xcellerate III Process. This clinical protocol was recently amended to allow patients to receive a 2nd infusion of Xcellerated T Cells. To date, 2nd products have been manufactured for 11 of the CLL patients using the original PBMC that had been stored cryopreserved for up to 7 months from collection. Comparison of the processes for the manufacture of 1st (n=13) and 2nd (n=11) infusion products shows: • No significant difference in the in-process T cell activation as determined by increase in cell size, up-regulation of CD25 & up-regulation of CD154 expression (refer to Figure 1). Figure Figure • The total cell yield for 2nd infusion products is within one (1) standard deviation of the average for the manufacture of the 1st infusion product (refer to Table 1). • No significant difference in cell viability, CD3+ purity, or CD4:CD8 ratio for the final Xcellerated T Cells product (refer to Table 1). Table 1. Final Product Characteristics Final Product (Day 13) Average±S.D. p value 1st Infusion (n=13) 2nd Infusion (n=11) Total Cell Yield (x109) 0.01 137 ± 35 104 ± 17 Cell Viability (%) 0.15 93.5 ± 3.4 91.6 ± 2.4 CD3+ Purity (%) <0.001 98.4 ± 1.1 99.0 ± 0 CD4:CD8 Ratio 0.32 8.5 ± 7.7 5.7 ± 4.5 These data demonstrate high reproducibility and robustness of the Xcellerate III Process when using PBMC from the same leukapheresis collection in sequential processing runs. In addition, these data demonstrate that cryopreserved PBMC can be stored for many months prior to their use as the starting material in the Xcellerate III Process. Xcyte™, Xcyte Therapies™, Xcellerate™, Xcellerated T Cells™ and the circle logo are trademarks of Xcyte Therapies, Inc.

Immunological impact of ramucirumab on tumor microenvironment in advanced gastric cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 98-98 ◽  
Author(s):  
Yosuke Togashi ◽  
Yasuko Tada ◽  
Daisuke Kotani ◽  
Akihito Kawazoe ◽  
Toshihiko Doi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Advanced Gastric Cancer ◽  
Mononuclear Cells ◽  
Low Frequency ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Peripheral Blood Mononuclear ◽  
Primary Tumors ◽  
Significant Difference

98 Background: Ramucirumab (RAM), a monoclonal antibody against VEGFR2, was recently approved for the treatment of advanced gastric cancer (GC). However, little is known about the immunological effects in advanced GC patients. Methods: Patients with advanced GC who had been planned to receive chemotherapy containing RAM were prospectively enrolled for this study from January 2016 to September 2016. Paired samples were obtained from peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TILs) in primary tumors pre- and post-RAM therapy to investigate immune profiles. Results: A total of 59 PBMCs and TILs from 18 patients were collected. Higher frequencies of FOXP3highCD45RA-CD4+ T cells (effector regulatory T cells: eTregs) were detected in TILs compared with PBMCs (19.05±10.48% vs 1.89±1.0%, P < 0.0001), and the presence of high eTreg in TILs was not reflected in PBMCs. eTregs of TILs, but not of PBMC were significantly decreased after RAM-containing therapies (22.67±11.19% vs. 16.33±8.44%, P = 0.034). Expressions of immune checkpoint (IC) molecules (PD-1, CTLA-4, LAG-3, and ICOS) were much higher in TILs than those in PBMCs, and all these molecules exhibited higher expressions on eTregs than on CD8+ T cells. Among them, ICOS was specifically expressed by eTregs in TILs. PD-1+CD8+ T cells in TILs were significantly decreased after RAM-containing therapies (54.99±19.06% vs. 39.23±17.15%, P = 0.0005), but not in PBMC. Patients with partial responses had significantly higher frequency of eTreg in pre-treatment TIL than those with progression disease (32.56±12.11% vs. 14.83±3.18%, P = 0.036). Furthermore, patients with high eTreg frequency had significantly longer progression-free survival than those with low frequency (161 days vs. 76 days, P = 0.024). Conclusions: There was significant difference in immune profile between PBMC and TIL in GC patients. eTregs and PD-1 expression on CD8+T cells in TILs, not in PBMCs were decreased after RAM-containing therapies. This observation suggests the importance of TIL analyses and might be a rationale to use RAM as an immunomodulator in combination with IC inhibitors.

scholarly journals dmLT Adjuvant Enhances Cytokine Responses to T Cell Stimuli, Whole Cell Vaccine Antigens and Lipopolysaccharide in Both Adults and Infants

2021 ◽  
Vol 12 ◽  
Author(s):  
Marjahan Akhtar ◽  
Nuder Nower Nizam ◽  
Salima Raiyan Basher ◽  
Lazina Hossain ◽  
Sarmin Akter ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Dose Range ◽  
Cell Vaccine ◽  
Adjuvant Effect ◽  
Adjuvant Activity ◽  
Peripheral Blood Mononuclear ◽  
Whole Cell ◽  
Age Related

Enhancement of mucosal immune responses in children and infants using novel adjuvants such as double mutant heat labile toxin (dmLT) is an important goal in the enteric vaccine field. dmLT has been shown to enhance mucosal IgA responses to the oral inactivated enterotoxigenic Escherichia coli (ETEC) vaccine ETVAX. dmLT can enhance IL-17A production from adult T cells, which may increase the production and secretion of mucosal IgA antibodies. However, the adjuvant mechanism remains to be fully elucidated and might differ between infants and adults due to age-related differences in the development of the immune system. The main objective of this study was to determine how dmLT influences antigen presenting cells and T cells from infants compared to adults, and the role of IL-1β for mediating the adjuvant activity. Peripheral blood mononuclear cells (PBMCs) from Bangladeshi infants (6-11 months) and adults (18-40 years) were stimulated with the mitogen phytohaemagglutinin (PHA), the superantigen Staphylococcal enterotoxin B (SEB), ETVAX whole cell component (WCC) or E. coli lipopolysaccharide (LPS) ± dmLT, and cytokine production was measured using ELISA and electrochemiluminescence assays. The adjuvant dmLT significantly enhanced SEB- and PHA-induced IL-17A, but not IFN-γ responses, in PBMCs from both infants and adults. Blocking experiments using an IL-1 receptor antagonist demonstrated the importance of IL-1 signaling for the adjuvant effect. dmLT, ETVAX WCC and LPS induced dose-dependent IL-1β responses of comparable magnitudes in infant and adult cells. Depletion experiments suggested that IL-1β was mainly produced by monocytes. dmLT enhanced IL-1β responses to low doses of WCC and LPS, and the adjuvant effect appeared over a wider dose-range of WCC in infants. dmLT and WCC also induced IL-6, IL-23 and IL-12p70 production in both age groups and dmLT tended to particularly enhance IL-23 responses to WCC. Our results show that dmLT can induce IL-1β as well as other cytokines, which in turn may enhance IL-17A and potentially modulate other immunological responses in both infants and adults. Thus, dmLT may have an important function in promoting immune responses to the ETVAX vaccine, as well as other whole cell- or LPS-based vaccines in infants in low- and middle-income countries.

Generation of CD8+ Viral Specific T Cells from EBV and CMV Naive Individuals.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3655-3655
Author(s):  
Lei Bao ◽  
Nargisa Niyazova-Brewer ◽  
Kimberly Dunham ◽  
Kenneth Kenneth ◽  
Qi Sun
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Memory T Cells ◽  
Ex Vivo ◽  
Peripheral Blood Mononuclear ◽  
Cell Clones ◽  
Cell Immunotherapy ◽  
Blood Mononuclear Cells ◽  
T Cell Immunotherapy

Abstract Adoptive T cell immunotherapy (ATCI) with viral specific T cells, as exemplified by ATCI against Epstein-Bar virus (EBV) and Cytomegalovirus (CMV) with viral specific T cells generated from virus-experienced individuals, is efficacious against viral reactivation in immuno-compromised hosts. EBV-seronegative solid organ transplant recipients and CMV-seropositive stem cell transplant patients receiving CMV-seronegative grafts are at high risk of EBV-driven lymphoproliferation and CMV reactivation, respectively. However, due to the absence of virus-specific memory T cells, ex vivo techniques for generating virus-specific CD8+ CTL from virus-naive individuals remain to be developed for reproducibility and efficiency. To extend ATCI to the above patients, we are developing novel ex vivo systems to expand virus specific CD8+ CTL from seronegative individuals. We designed a two step stimulation for the naive T cells to develop into specific T cells. The first step, “de-naiviation”, involves non-specific but high-affinity stimulation of CD45RO/CD25/CD56/CD14 depleted peripheral blood mononuclear cells with anti-CD3 and -CD28 antibodies. The “de-naiviated” T cells were then antigen-specifically stimulated by antigen presenting cells expressing both EBV and CMV antigens. Peripheral blood mononuclear cells from an EBV/CMV seronegative individual were depleted for two rounds with micro-beads conjugated with antibodies against CD45RO, CD25, CD14 and CD56. The resultant cells were a homogenous population of cells mostly CD45RO−/CD45RA+/CD3+/CD25−, the phenotype for naïve T cells. After a period of expansion stimulated by a cocktail containing anti-CD3 (OKT3) and -CD28, 90% of the RO-T cells became RO+/RA−, the phenotype of memory T cells. Nearly all the CD4+ cells and most the CD8 cells became CD25+, suggesting recent activation. Then the “de-naiviated” T cells were stimulated with autologous EBV immortalized B lymphoblastoid cells transduced and expressing the CMV pp65 (CMVpp65) antigen. After three rounds of stimulation, the T cells were screened for specific production of interferon-gamma (IFNg) by ELISA. Clones were isolated from the primed T cells, and FACS analysis showed that the T cell clones produced IFNg in response to EBV BLCL expressing CMVpp65. These T cells also antigen-specificly expressed IL2 and GMCSF. Interestingly, while the cells were predominantly CD8+/CD3+, some of the cells were also positive for CD56, suggesting newly differentiated effector T cells. Work is ongoing to further characterize the T cell clones for antigen specificity, functionality and differentiation status. The novel approach we are developing has the potential to generate EBV and CMV specific CD8+ CTL from virus naive individuals for adoptive T cell immunotherapy against viral infections.

scholarly journals Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts

2020 ◽  
Author(s):  
Pedro Henrique Ferreira Marçal ◽  
Rafael Silva Gama ◽  
Lorena Bruna de Oliveira Pereira ◽  
Olindo Assis Martins Filho ◽  
Roberta Olmo Pinheiro ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Clinical Status ◽  
T Cell Subsets ◽  
Diagnostic Tools ◽  
Peripheral Blood Mononuclear ◽  
Household Contacts ◽  
Leprosy Patients

Abstract Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: paucibacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to detect subclinical leprosy in household contacts. Methods: The main goal of the present study was to characterize the global cytokine signatures of CD4+ and CD8+ T-cells from leprosy patients with distinct clinical forms and their respective household contacts (HHC) upon in vitro antigen-specific stimuli. Short-term culture of peripheral blood mononuclear cells was done. After incubation, cells were harvested and prepared for surface and intracytoplasmic cytokine staining Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-g+ T-cell subsets along with IL-10+ and IL-4+ from CD4+ T-cells. Moreover, L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-g+, IL-10+ and IL-4+ produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10+ and IL-4+ T-cells with minor contribution of IFN-g produced by CD4+ T-cells. Noteworthy was that HHC(MB) exhibited enhanced frequency of IFN-g+ T-cells, contrasting with HHC(PB) that presented a cytokine profile limited to IL-10 and IL-4. Conclusions: Together, our findings provide additional immunological features associated with leprosy and household contacts. These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts may present subclinical infection.

scholarly journals Expression of inhibitory receptors on CD4+ and CD8+ T cells from healthy Colombian donors

2012 ◽  
Vol 17 (1) ◽  
pp. 35
Author(s):  
Alejandra Rico- Lombana Rico- Lombana ◽  
Jose Mateus ◽  
Paola Lasso ◽  
John Mario González ◽  
Concepción Judith Puerta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Inhibitory Receptors ◽  
Peripheral Blood Mononuclear ◽  
Programmed Death ◽  
Significant Difference ◽  
Programmed Death 1

<p>T cell activation involves positive cellular signals that promote effector functions and negative signals that contribute to the regulation of these responses. These regulatory signals are generated upon activation of receptors on T cells that include CD160, 2B4, Programmed Death-1 and CTLA-4. <strong>Objective</strong>. To evaluate the expression of inhibitory receptors like CD160, 2B4, Programmed Death-1 and CTLA-4 on CD4+ and CD8+ T cells from healthy Colombian donors. <strong>Materials and methods</strong>. Peripheral blood mononuclear cells from 30 healthy donors from Bogotá (Colombia) were obtained via Ficoll-Hypaque density gradient and cells were stained with specific conjugated antibodies previously titrated. <strong>Results</strong>. The CD160, 2B4, and Programmed Death-1 inhibitory markers were detected on CD4+ T cells<br />with expression levels of 0.35%, 1.04%, and 1.35%, respectively. On CD8+ T cells, these markers were expressed at higher levels: 16%, 8.97%, and 4.3%, respectively. In contrast to the other receptors, CTLA-4 frequency of expression showed no significant difference between CD4+ (1.56%) and CD8+ (1.53%) T cells. Frequency of CD160/2B4 and CTLA-4/ Programmed Death-1 coexpression was 0.18% and 0.09% on CD4+ cells, and 4.02% and 0.2% on CD8+ T cells. <strong>Conclusions</strong>. This is the first report showing the frequency of inhibitory receptors such as CD160, 2B4, Programmed Death-1, and CTLA-4 on CD4+ and CD8+ T cells from healthy Colombian donors. Our findings serve as a baseline for the analysis and comparison of these receptors in Colombian populations with different disease conditions.</p><p><br /><strong>Key words</strong>: inhibitory receptors, T cells</p>

scholarly journals TLR7 and RIG-I dual-adjuvant loaded nanoparticles drive broadened and synergistic responses in dendritic cells in vitro and generate unique cellular immune responses in influenza vaccination

2020 ◽  
Author(s):  
Randall Toy ◽  
M. Cole Keenum ◽  
Pallab Pradhan ◽  
Katelynn Phang ◽  
Patrick Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mouse Bone Marrow ◽  
Peripheral Blood Mononuclear ◽  
Flu Vaccination

ABSTRACTAlthough the existing flu vaccines elicit strong antigen-specific antibody responses, they fail to provide effective, long term protection – partly due to the absence of robust cellular memory immunity. We hypothesized that co-administration of combination adjuvants, mirroring the flu-virus related innate signaling pathways, could elicit strong cellular immunity. Here, we show that the small molecule adjuvant R848 and the RNA adjuvant PUUC, targeting endosomal TLR7s and cytoplasmic RLRs respectively, when delivered together in polymer nanoparticles (NP), elicits a broadened immune responses in mouse bone marrow-derived dendritic cells (mBMDCs) and a synergistic response in both mouse and human plasmacytoid dendritic cells (pDCs). In mBMDCs, NP-R848-PUUC induced both NF-κB and interferon signaling. Interferon responses to co-delivered R848 and PUUC were additive in human peripheral blood mononuclear cells (PBMCs) and synergistic in human FLT3-differentiated mBMDCs and CAL-1 pDCs. Vaccination with NPs loaded with H1N1 Flu antigen, R848, and PUUC increased percentage of CD8+ T-cells in the lungs, percentage of antigen-specific CD4+T-cells in the spleen, and enhanced overall cytokine-secreting T cell percentages upon antigen restimulation. Also in the spleen, T lymphopenia, especially after in vitro restimulation, was observed. Our results demonstrate that simultaneous engagement of TLR7 and RIG-I pathways using particulate carriers is a potential approach to improve cellular immunity in flu vaccination.GRAPHICAL ABSTRACT

scholarly journals Humoral and Cellular Immune Responses to Yersinia pestis Infection in Long-Term Recovered Plague Patients

2011 ◽  
Vol 19 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Bei Li ◽  
Chunhong Du ◽  
Lei Zhou ◽  
Yujing Bi ◽  
Xiaoyi Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Mononuclear Cells ◽  
Vaccine Development ◽  
Effective Vaccine ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Cellular Immune Responses ◽  
Significant Difference ◽  
Cellular Immune

ABSTRACTPlague is one of the most dangerous diseases and is caused byYersinia pestis. Effective vaccine development requires understanding of immune protective mechanisms against the bacterium in humans. In this study, the humoral and memory cellular immune responses in plague patients (n= 65) recovered fromY. pestisinfection during the past 16 years were investigated using a protein microarray and an enzyme-linked immunosorbent spot assay (ELISpot). The seroprevalence to the F1 antigen in all recovered patients is 78.5%. In patients infected more than a decade ago, the antibody-positive rate still remains 69.5%. There is no difference in the antibody presence between gender, age, and infected years, but it seems to be associated with the F1 antibody titers during infection (r= 0.821;P< 0.05). Except F1 antibody, the antibodies against LcrV and YopD were detected in most of the patients, suggesting they could be the potential diagnostic markers for detecting the infection of F1-negative strains. Regarding cellular immunity, the cell number producing gamma interferon (IFN-γ), stimulated by F1 and LcrV, respectively,in vitroto the peripheral blood mononuclear cells of 7 plague patients and 4 negative controls, showed no significant difference, indicating F1 and LcrV are not dominant T cell antigens against plague for a longer time in humans. Our findings have direct implications for the future design and development of effective vaccines againstY. pestisinfection and the development of new target-based diagnostics.

Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses

Blood ◽  
2008 ◽  
Vol 111 (12) ◽  
pp. 5610-5620 ◽  
Author(s):  
Madeleine M. Hipp ◽  
Norbert Hilf ◽  
Steffen Walter ◽  
Daniela Werth ◽  
Katharina M. Brauer ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Map Kinases ◽  
Kinase Inhibitors ◽  
Mononuclear Cells ◽  
Cytotoxic T Cell ◽  
Peripheral Blood Mononuclear

AbstractThe tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhibitory effects are mediated by inhibition of PI3 and MAP kinases and NFκB signaling. In contrast, sorafenib had no influence on the phenotype and proliferation of T cells. To analyze the effects of both TKIs on cytotoxic T-cell induction in vivo, C57BL/6 mice were pretreated with sorafenib or sunitinib and immunized with OVA257-264 peptide. Sorafenib, but not sunitinib, application significantly reduced the induction of antigen-specific T cells. Numbers of regulatory T cells were reduced in peripheral blood mononuclear cells from mice treated with sunitinib. These results indicate that sunitinib, but not sorafenib, is suitable for combination with immunotherapeutic approaches for treatment of cancer patients.

scholarly journals Single-cell RNA sequencing of peripheral blood mononuclear cells from acute Kawasaki disease patients

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhen Wang ◽  
Lijian Xie ◽  
Guohui Ding ◽  
Sirui Song ◽  
Liqin Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Kawasaki Disease ◽  
Immune Responses ◽  
Single Cell ◽  
Rna Sequencing ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Single Cell Rna Sequencing ◽  
Blood Mononuclear Cells

AbstractKawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased. The percentage of CD8+ T cells is decreased in acute KD, notably effector memory CD8+ T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.

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