scholarly journals BpOmpW Antigen Stimulates the Necessary Immune Correlates of Protection Against Melioidosis

2021 ◽  
Author(s):  
Julen Tomas-Cortazar ◽  
Siobhan McClean
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Nkt Cells ◽  
Control Group ◽  
Insulin Resistant ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Hla Dq

Melioidosis is a fatal disease caused by Burkholderia pseudomallei Gram-negative bacteria. It is the causative of 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. Diabetes mellitus is the most risk factor, increasing 12-fold the susceptibility for severe disease. IFN-y responses from CD4 and CD8 T cells, but also from NK and NKT cells are necessary to eliminate the pathogen. Elucidating the immune correlates of protection of our previously described protective BpOmpW vaccine is an essential step of any vaccine before clinical trials. Thus, we immunized non-insulin resistant C57BL/6j mice and an insulin resistant C57BL/6j mouse model of Type 2 Diabetes (T2D) with BpOmpW using Sigma Adjuvant System (SAS) (treatment) or SAS only (control). Two weeks later bloods and spleens were collected and serological analysis & in vitro exposure of splenocytes to the antigen for 60 hours were performed in both controls and treatment groups to finally analyze the stained splenocytes by flow cytometry. BpOmpW induced strong antibody response, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+regulatory T cells and produced higher IFN-y; responses in CD4+, CD8+, NK and NKT cells relative to the control group in non-insulin resistant mice. T cell responses of insulin resistant mice to BpOmpW were comparable to those in non-insulin resistant mice. In addition, as a precursor to its evaluation in human studies, humanised HLA-DR and HLA-DQ transgenic mice elicited IFN-y; recall responses in an ELISPoT-based study and PBMCs from donors that were in contact to BpOmpW for seven days experienced T cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, these range of approaches used strongly indicate that BpOmpW elicits the required immune correlates of protection to combat melioidosis and bring the vaccine closer to clinical trials.

scholarly journals BpOmpW Antigen Stimulates the Necessary Protective T-Cell Responses Against Melioidosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Julen Tomás-Cortázar ◽  
Lorenzo Bossi ◽  
Conor Quinn ◽  
Catherine J. Reynolds ◽  
David K. Butler ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
T Cell Responses ◽  
Nkt Cells ◽  
Insulin Resistant ◽  
Cell Responses ◽  
Hla Dq ◽  
Ifn Γ

Melioidosis is a potentially fatal bacterial disease caused by Burkholderia pseudomallei and is estimated to cause 89,000 deaths per year in endemic areas of Southeast Asia and Northern Australia. People with diabetes mellitus are most at risk of melioidosis, with a 12-fold increased susceptibility for severe disease. Interferon gamma (IFN-γ) responses from CD4 and CD8 T cells, but also from natural killer (NK) and natural killer T (NKT) cells, are necessary to eliminate the pathogen. We previously reported that immunization with B. pseudomallei OmpW (BpOmpW antigen) protected mice from lethal B. pseudomallei challenge for up to 81 days. Elucidating the immune correlates of protection of the protective BpOmpW vaccine is an essential step prior to clinical trials. Thus, we immunized either non-insulin-resistant C57BL/6J mice or an insulin-resistant C57BL/6J mouse model of type 2 diabetes (T2D) with a single dose of BpOmpW. BpOmpW induced strong antibody responses, stimulated effector CD4+ and CD8+ T cells and CD4+ CD25+ Foxp3+ regulatory T cells, and produced higher IFN-γ responses in CD4+, CD8+, NK, and NKT cells in non-insulin-resistant mice. The T-cell responses of insulin-resistant mice to BpOmpW were comparable to those of non-insulin-resistant mice. In addition, as a precursor to its evaluation in human studies, humanized HLA-DR and HLA-DQ (human leukocyte antigen DR and DQ isotypes, respectively) transgenic mice elicited IFN-γ recall responses in an enzyme-linked immune absorbent spot (ELISpot)-based study. Moreover, human donor peripheral blood mononuclear cells (PBMCs) exposed to BpOmpW for 7 days showed T-cell proliferation. Finally, plasma from melioidosis survivors with diabetes recognized our BpOmpW vaccine antigen. Overall, the range of approaches used strongly indicated that BpOmpW elicits the necessary immune responses to combat melioidosis and bring this vaccine closer to clinical trials.

scholarly journals DC-Based Vaccines for Cancer Immunotherapy

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 706
Author(s):  
Chunmei Fu ◽  
Li Zhou ◽  
Qing-Sheng Mi ◽  
Aimin Jiang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Critical Role ◽  
Cd8 T Cell ◽  
T Cell Immunity ◽  
Cell Responses ◽  
Cell Immunity

As the sentinels of the immune system, dendritic cells (DCs) play a critical role in initiating and regulating antigen-specific immune responses. Cross-priming, a process that DCs activate CD8 T cells by cross-presenting exogenous antigens onto their MHCI (Major Histocompatibility Complex class I), plays a critical role in mediating CD8 T cell immunity as well as tolerance. Current DC vaccines have remained largely unsuccessful despite their ability to potentiate both effector and memory CD8 T cell responses. There are two major hurdles for the success of DC-based vaccines: tumor-mediated immunosuppression and the functional limitation of the commonly used monocyte-derived dendritic cells (MoDCs). Due to their resistance to tumor-mediated suppression as inert vesicles, DC-derived exosomes (DCexos) have garnered much interest as cell-free therapeutic agents. However, current DCexo clinical trials have shown limited clinical benefits and failed to generate antigen-specific T cell responses. Another exciting development is the use of naturally circulating DCs instead of in vitro cultured DCs, as clinical trials with both human blood cDC2s (type 2 conventional DCs) and plasmacytoid DCs (pDCs) have shown promising results. pDC vaccines were particularly encouraging, especially in light of promising data from a recent clinical trial using a human pDC cell line, despite pDCs being considered tolerogenic and playing a suppressive role in tumors. However, how pDCs generate anti-tumor CD8 T cell immunity remains poorly understood, thus hindering their clinical advance. Using a pDC-targeted vaccine model, we have recently reported that while pDC-targeted vaccines led to strong cross-priming and durable CD8 T cell immunity, cross-presenting pDCs required cDCs to achieve cross-priming in vivo by transferring antigens to cDCs. Antigen transfer from pDCs to bystander cDCs was mediated by pDC-derived exosomes (pDCexos), which similarly required cDCs for cross-priming of antigen-specific CD8 T cells. pDCexos thus represent a new addition in our arsenal of DC-based cancer vaccines that would potentially combine the advantage of pDCs and DCexos.

Prolonged Thrombocytopenia After Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) and Its Association with an Increase in CD8+ CX3CR1+ Cells in Bone Marrow.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3077-3077
Author(s):  
Xiao-hui Zhang ◽  
Guo-xiang Wang ◽  
Yan-rong Liu ◽  
Lan-Ping Xu ◽  
Kai-Yan Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Surface Expression ◽  
T Cell Subsets ◽  
Control Group ◽  
Hematopoietic Stem ◽  
Cell Counts

Abstract Abstract 3077 Background: Since prolonged thrombocytopenia (PT) is an independent risk factor for poor clinical outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the underlying mechanisms need to be understood in order to develop selective treatments. Previous studies1–4 have suggested that abnormalities in B cells may play a role in the pathogenesis of PT. However, abnormalities in B cells alone do not fully explain the complete pathogenic mechanisms of PT. Our previous studies5 showed that the frequency of megakaryocytes with a ploidy value ≤ 8N was significantly increased in patients who developed PT after allo-HSCT compared to the control group. Mechanisms concerning the megakaryocyte hypoplasia in PT after allo-HSCT are not well understood. Design and Methods: PT was defined as a platelet count ≤80 × 109/L for more than 3 months after HSCT, recovery of all other cell counts, and no apparent cause for thrombocytopenia, such as aGVHD, disease recurrence, CMV infection, or antiviral drug treatment at three months post-HSCT when all other blood cell counts had return to normal.5 We analyzed T cell subsets in bone marrow (BM) and peripheral blood (PB) from allo-HSCT recipients with and without PT (n = 23 and 17, respectively) and investigated the expression characteristics of homing receptors CX3CR1, CXCR4 and VLA-4 by flow cytometry. Futhermore, Mononuclear cells (MNCs) from PT patients and controls were cultured with and without autologous CD8+ T cells in vitro, and clarify the effect of activated CD8+ T cells on the ploidy and apoptosis of megakaryocytes in the bone marrow. Results: The results demonstrated that the percentage of CD3+ T cells in the BM was significantly higher in PT patients than the experimental controls (76.00 ± 13.04% and 57.49 ± 9.11%, respectively, P < 0.001), whereas this difference was not significant for the PB (71.01 ± 11.49% and 70.49 ± 12.89%, respectively, P = 0.911). While, some T cell subsets in the BM and PB from allo-HSCT recipients with PT were not significantly different from that of the experimental control group, such as CD8+ T cells, CD4+ T cells, CD4+ CD25bright T cells (regulatory T cells), CD44hi CD62Llo CD8+ T cells and naive T cells (CD11a+ CD45RA+). Furthermore, the surface expression of homing receptor CX3CR1 on BM T cells (64.16 ± 14.07% and 37.45 ± 19.66%, respectively, P < 0.001) and CD8+ T cells (56.25 ± 14.54% and 35.16 ± 20.81%, respectively, P = 0.036), but not in blood, were significantly increased in PT patients compared to controls. For these two groups of patients, the surface expression of CXCR4 and VLA-4 on T cells and CD8+ T cells from both BM and PB did not show significant differences. Through the study in vitro, we found that the activated CD8+ T cells in bone marrow of patients with PT might suppress apoptosis (MNC group and Co-culture group: 18.02 ± 3.60% and 13.39 ± 4.22%, P < 0.05, respectively) and Fas expression (MNC group and Co-culture group: 21.10 ± 3.93 and 15.10 ± 2.33, P <0.05, respectively) of megakaryocyte. In addition, megakaryocyte with a ploidy value ≤ 8N (MNC group: 40.03 ± 6.42% and 24.54 ± 4.31%, respectively, P < 0.05) was significantly increased in patients with PT compared to the control group. Conclusions: In conclusion, an increased surface expression of CX3CR1 on T cells may mediate the recruitment of CD8+ T cells into the bone marrow in patients with PT who received an allo-HSCT. Moreover, CD8+CX3CR1+ T cells, which can have significantly increased numbers in bone marrow of patients with PT, likely caused a reduction in the megakaryocyte ploidy, and suppressed megakaryocyte apoptosis via CD8+ T cell-mediated cytotoxic effect, possibly leading to impaired platelet production. Therefore, treatment targeting CX3CR1 should be considered as a reasonable therapeutic strategy for PT following allo-HSCT. Disclosures: No relevant conflicts of interest to declare.

NKT cells and CD8+ T cells are dispensable for T cell dependent allergic airway inflammation

2007 ◽  
Author(s):  
Jyoti Das ◽  
Paul Eynott ◽  
Luc Van Kaer ◽  
Yufang Shi ◽  
Gobardhan Das
Keyword(s):  
T Cells ◽  
T Cell ◽  
Airway Inflammation ◽  
Cd8 T Cells ◽  
Allergic Airway Inflammation ◽  
Nkt Cells

Elevated Expression of T-Cell Immunoglobulin and Mucin Domain 3 on T Cells from Peripheral Blood in Patients with Cervical Carcinoma

2020 ◽  
pp. 1-8
Author(s):  
Juan Li ◽  
Xiao-fei Sun ◽  
Ying Shen ◽  
Qing Yang ◽  
Shu-yan Dai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cervical Carcinoma ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Control Group ◽  
Healthy Controls ◽  
Novel Therapy ◽  
Domain 3

<b><i>Objective:</i></b> To investigate the expression of T-cell immunoglobulin and mucin domain 3 (TIM-3) on peripheral T cells of cervical carcinoma patients. <b><i>Methods:</i></b> Peripheral blood samples from 15 high-grade cervical squamous intraepithelial lesion (HSIL) patients, 24 cervical carcinoma patients, and 21 healthy controls were collected. TIM-3 expressions on the surface of peripheral CD4+ T cells and CD8+ T cells were analyzed with flow cytometry. <b><i>Results:</i></b> There was significantly lower expression of CD4+ T cells and CD8+ T cells in HSIL patients and cervical carcinoma patients compared with healthy controls. We also found that TIM-3 expression on peripheral CD4+ T and CD8+ T cells of both HSIL patients and cervical carcinoma patients was significantly increased compared to the control group. Further analyses revealed that the expression of TIM-3 on peripheral CD4+ T and CD8+ T cells significantly increased in stage III–IV cervical carcinoma patients compared to stages I–II. <b><i>Conclusion:</i></b> The increased expression of TIM-3 on CD4+ T cells and CD8+ T cells of patients with cervical carcinoma and HSIL suggests the potential role of TIM-3 in the development and progression of cervical carcinoma, which may be a novel therapy target for cervical carcinoma.

scholarly journals Natural Killer T Cell Ligand α-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines

2002 ◽  
Vol 195 (5) ◽  
pp. 617-624 ◽  
Author(s):  
Gloria Gonzalez-Aseguinolaza ◽  
Luc Van Kaer ◽  
Cornelia C. Bergmann ◽  
James M. Wilson ◽  
John Schmieg ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Viral Infections ◽  
Tumor Development ◽  
Nkt Cells ◽  
Cell Mediated Immunity ◽  
Natural Killer T

The important role played by CD8+ T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8+ T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, α-galactosylceramide (α-GalCer), causes bystander activation of NK, B, CD4+, and CD8+ T cells. Our study shows that coadministration of α-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of α-GalCer with various different immunogens strongly enhances antigen-specific CD8+ T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of α-GalCer require CD1d molecules, Vα14 NKT cells, and interferon γ. As α-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.

Effect of Melan-Α/Μart-1-peptide vaccination plus IMP321 on antitumor immunity and clinical benefit in patients receiving autologous PBMCs after lymphodepletion.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20011-e20011
Author(s):  
Emanuela Romano ◽  
Helene Bichat ◽  
Athina Stravodimou ◽  
Pedro Romero ◽  
Speiser E Daniel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Clinical Benefit ◽  
Fold Increase ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Great Promise ◽  
Control Group ◽  
Significant Difference

e20011 Background: Immunotherapy offers great promise for cancer treatmet. Strong evidence supports adoptive cell transfer (ACT) and immunemodulation for regression of advanced melanoma. Few studies assessed the potential synergy between these two strategies. Methods: Twelve patients with metastatic melanoma received multiple Melan-A/Mart-1-peptide vaccinations with (n=6) or without (n=6) IMP321 (LAG-3Ig fusion protein) as an adjuvant in combination with lymphodepleting chemotherapy and ACT. All patients were selected on the basis of ex vivo detectable Melan-A-specific CD8 T cell responses and were immunized at day (D) 0, 8, 15, 22, 28, 52, and 74 post-reinfusion. Results: One-week after reinfusion of bulk autologous PBMCs, a significant expansion of Melan-A-specific CD8 T cells was measured in >83% (n=5) and <17% (n=1) of patients from the IMP321 and control groups, respectively (p=0.02). Compared to the control group, the mean fold increase of Melan-A-specific CD8 T cells was respectively >2-, >4-, and >6-fold higher in the IMP321 group at D15, D30, and D60 (p=0.02). A long-lasting Melan-A-specific CD8 T-cell response was significantly associated with IMP321 (p<0.001). A higher proportion of Melan-A-specific CD8 TEMRA (i.e., CD45RA+CCR7-CD127-) cells was observed in the IMP321 group at the peak of the response (p <0.002), whereas no significant difference was observed in the expression of co-inhibitory receptors (i.e., PD-1, 2B4, TIM3, CD160). IMP321 was associated with a significantly (p<0.04) reduced expansion of regulatory T cells (TREGS); we observed a negative correlation between the fold increase of Melan-A-specific CD8 T cells and the relative expansion of TREGS. Clinical benefit (assessed as CR, PR, and SD) was observed in none of the control patients vs 67% (4/6) of patients from the IMP321 group, (p=0.02). Conclusions: Vaccination with IMP321 as an adjuvant in combination with lymphodepleting chemotherapy and ACT provided clinical benefit and this was associated with a more robust and durable cellular antitumor immune response, supporting further development of IMP321 for future immunotherapeutic strategies. Clinical trial information: NCT00324623.

scholarly journals Arsenic Trioxide Encapsulated in MSC-Derived Extracellular Vesicles: A Novel Therapy for aGVHD in Mice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5673-5673
Author(s):  
Xiao Liu ◽  
Ya-Nan Wang ◽  
Gao-chao Zhang ◽  
Yan Su ◽  
Qiu-sha Huang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Treatment Group ◽  
Arsenic Trioxide ◽  
Extracellular Vesicles ◽  
Cd8 T Cells ◽  
Notch Pathway ◽  
Control Group ◽  
Tnf Α ◽  
Ifn Γ

Abstract Introduction: Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation. Mesenchymal stem cells (MSCs) can modulate immune response and have been used as a treatment for aGVHD. The immune-modulating factors of MSCs are secreted and reside in supernatant fractions that are enriched for extracellular vesicles (EVs). MSC-derived EVs (MSC-EVs) also exhibit immunosuppressive activity, providing many advantages compared to MSCs and have been proven therapeutic in aGVHD. Arsenic trioxide (ATO) exhibits potent antitumor effects and increasing studies indicate its immunosuppressive effects. However, ATO at high concentrations can cause severe adverse effects. If encapsulated in some kind of drug vehicles, ATO can be made less toxic. Therefore, we believed that the combination of MSC-EVs with a low dose of ATO would be an effective therapy for aGVHD. Methods: We used a classical GVHD model (BALB/c→B6) and developed 4 groups: the control group (TCD-BM), the GVHD control group (TCD-BM + spleen T cells), the MSC-EVs treatment group and the MSC-ATO-EVs (MSC-derived ATO-encapsulating EVs) treatment group. OS, GVHD clinical and histological scores were evaluated. A20-luc lymphoma cells were injected to generate the GVL model. Using flow cytometry analysis, we analyzed Th cell subsets, cytokines and transcription factors (Th1*IFN-γ/TNF-α*T-bet, Th2*IL-4*GATA3, Th17*IL-17*RORγt, Treg*IL-10*Foxp3) and sorted CD8+ SLECs, and CD8+ MPECs in BM and spleen of recipients. Dll4 expression was analyzed on DCs. B6 cells were incubated with or without BALB/c spleen cells and complete medium alone, with 10 mM ATO alone. T cell apoptosis was determined with Yopro-1 staining. We used MLR assays to examine Th subsets, cytokines and notch targeted genes with or without ATO or neutralizing Ab specific to Dll4 (anti-Dll4). Results: BALB/c mice receiving B6 TCD-BM alone developed no sign of GVHD, whereas all BALB/c mice receiving B6 donor TCD-BM + spleen T cells died of GVHD. In contrast, injection of MSC-EVs and MSC-ATO-EVs inhibited GVHD in T cell recipients, with 20% and 29% of them surviving without severe GVHD, respectively. These survival rates were accompanied by significantly lower clinical and histological scores. GVL effects mediated by MSC-EVs and MSC-ATO-EVs were comparable to those obtained in the GVHD control group. Compared to the control group, CD4+T and CD8+T cells increased substantially in T cell recipients, resulting in severe GVHD. In contrast, treatment with MSC-ATO-EVs significantly reduced the number of CD4+T and CD8+T cells, while MSC-EVs recipients retained approximately the same number of T cells as the GVHD group. Compared to the GVHD control group, Th2 and Treg cells derived from the spleen increased, while Th1 and Th17 cells were reduced significantly in both the MSC-EVs and MSC-ATO-EVs groups. We also detected lower serum levels of TNF-α and IFNγ as well as lower expression of RORγt and T-bet in blood and BM CD4+ T cells in these two groups, while the expression of GATA3 and Foxp3 increased significantly. Treatment with MSC-ATO-EVs markedly raised the MPEC/SLEC ratio compared to the MSC-EVs and GVHD control groups. We also examined Dll4high DCs in different organs and different groups and found that only MSC-ATO-EVs significantly reduced the Dll4high DCs, especially in the spleen and intestine. Treatment of stimulated B6 CD4+ T and CD8+ T cells with ATO increased production of H2O2. Yopro-1 staining of activated B6 CD4+ T and CD8+ T cells indicated that ATO dramatically triggered apoptosis in those cells. DCs were isolated and cultured with B6 mouse-derived CD4+ T or CD8+ T cells, with or without addition of ATO or anti-Dll4. ATO and anti-Dll4 both led to significant reduction of IFN-γ and TNF-α, while IL-4 and IL-10 increased slightly. We next assessed the notch pathway targeted genes in T cells and found there were significantly increased GATA3 and reduced Dtx expression levels. Conclusion: Altogether, our findings demonstrate that MSC-ATO-EVs might be a highly promising therapy for aGVHD through reducing T cell amounts and modulating Th subsets and CD8+ T cell differentiation. These effects can be explained with the inhibition of the Dll4-notch pathway by ATO. Therefore, further exploitation of the potential application of ATO in aGVHD and the mechanisms of action of ATO may improve outcomes after allo-HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Observation of the Number of Lymphocytes and T Cell Subsets in Patients with COVID-19 at Different Stages

2020 ◽  
Author(s):  
Jing Bai ◽  
Hui Zhou ◽  
Bao-sheng Dai
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
White Blood Cells ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Subsets ◽  
Control Group ◽  
Cd8 Cells ◽  
Significant Difference ◽  
Severe Group

Abstract To explore the changes of lymphocytes and T cell subsets at different stages in patients with COVID-19. 86 patients with COVID-19 were enrolled, and the dynamic changes of peripheral blood lymphocytes and T cell subsets of CD3+, CD4+, and CD8+ were measured on admission, after treatment for1 week, 2 weeks, and before discharge. There were no significant differences in the number of white blood cells and lymphocytes between admission and 2 weeks after treatment or before discharge in severe patients. The counts of CD3+, CD4+, and CD8+ T cells decreased significantly on admission. After 2 weeks of treatment, the CD3+ counts were significantly higher than that on admission. The CD4+ and CD8+ counts increased significantly after 1 week of treatment, and went up remarkably before discharge compared with that on admission. There was no significant difference in the number of CD3+ cells between the mild group and the control group on admission, but it was significantly lower in the severe group than that in the control group and the mild group. The CD4+ and CD8+ counts decreased significantly in both mild and severe patients on admission, and increased significantly before discharge. At the time of discharge, the CD4+ counts in the severe and mild groups were still significantly lower than in the control group, but there was no significant difference in CD8+ counts among the three groups. The counts of CD3+,CD4+,and CD8+ T cells in the patients with COVID-19 is significantly correlated with the short-term prognosis, and is more sensitive than lymphocytes. In the earliest stage, the numbers of CD4+ and CD8+ cells are more sensitive to early reduction and faster to late recovery.

Dendritic Cell Vaccines Are Superior to Idiotype-KLH Protein Vaccines at Priming a Therapeutic, Tumor-Specific Immunity Against Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3466-3466
Author(s):  
Qing Yi ◽  
Siqing Wang ◽  
Michele Wezeman ◽  
Jianfei Qian ◽  
Jing Yang
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Tumor Cells ◽  
Cd8 T Cells ◽  
Myeloma Cells ◽  
Dc Vaccines ◽  
Ifn Γ ◽  
Protein Vaccines

Abstract Idiotype (Id) protein secreted by myeloma cells is the best-characterized tumor-specific antigen and has been used in clinical vaccination trials administered either as Id-keyhole limpet hemocyanin (KLH) protein vaccines or as Id-pulsed dendritic cell (DC) vaccines. In this study, we used the 5TGM1 myeloma murine model to compare the efficacy of Id-KLH (protein vaccines) versus DCs pulsed with Id-KLH (DC vaccines), two formulas commonly used in clinical trials, to induce tumor-specific immunity, to protect mice from developing myeloma, and to treat myeloma-bearing mice. Vaccinations consisted of three weekly, subcutaneous injections of the protein conjugates (100 μg/injection) or Id-KLH-pulsed, bone marrow-derived mature DCs (106 cells/injection). Following each vaccination, GM-CSF (200 ng/day/mouse) was injected subcutaneously (adjacent to the vaccination sites) for three consecutive days. We found that, although the protein vaccines induced significantly higher titers of specific antibodies, DC vaccines were superior at inducing tumor-specific, cellular immune responses, evident by increased IFN-γ production, T cell proliferation, and cytotoxic T cell activities against the tumor cells. As prophylactic treatments, protein and DC vaccines were equally efficient at protecting mice from subsequent tumor challenge. However, only DC vaccines induced therapeutic immunity in tumor-bearing mice: DC vaccinations not only retarded tumor growth but also eradicated established tumors in more than 50% of mice, which was associated with an induction of potent, tumor-specific type-1 (IFN-γ) and type-2 (IL-4) T-cell responses. DC-vaccinated mice also showed a more pronounced increase in the percentages of CD8+ T cells in their spleens after in vitro stimulation with irradiated myeloma cells and increased tumor-specific cytotoxicity in enriched CD8+ T cells over the whole splenic cells, suggesting that CD8+ T cells play a major role in killing tumor cells in vivo. Furthermore, surviving mice were also protected from rechallenge with the myeloma cells, indicating that memory T cells existed and were functional. Thus, our results show that Id-based DC vaccines may be a favorable vaccine for immunotherapy in MM. Further studies are required to optimize DC vaccination protocols to achieve therapeutic efficacy in clinical trials.

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