scholarly journals HIV Interferes with the Dendritic Cell–T Cell Axis of Macrophage Activation by ShiftingMycobacterium tuberculosis–Specific CD4 T Cells into a Dysfunctional Phenotype

2018 ◽  
Vol 202 (3) ◽  
pp. 816-826 ◽  
Author(s):  
Susmita K. Singh ◽  
Marie Larsson ◽  
Thomas Schön ◽  
Olle Stendahl ◽  
Robert Blomgran
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cd4 T Cells ◽  
Macrophage Activation ◽  
Cell Axis

scholarly journals The critical role of CD4+ T cells in PD-1 blockade against MHC-II–expressing tumors such as classic Hodgkin lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4069-4082
Author(s):  
Joji Nagasaki ◽  
Yosuke Togashi ◽  
Takeaki Sugawara ◽  
Makiko Itami ◽  
Nobuhiko Yamauchi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Cd4 T Cell ◽  
Antitumor Effects ◽  
Cell Axis ◽  
Mhc I ◽  
Mhc Ii

Abstract Classic Hodgkin lymphoma (cHL) responds markedly to PD-1 blockade therapy, and the clinical responses are reportedly dependent on expression of major histocompatibility complex class II (MHC-II). This dependence is different from other solid tumors, in which the MHC class I (MHC-I)/CD8+ T-cell axis plays a critical role. In this study, we investigated the role of the MHC-II/CD4+ T-cell axis in the antitumor effect of PD-1 blockade on cHL. In cHL, MHC-I expression was frequently lost, but MHC-II expression was maintained. CD4+ T cells highly infiltrated the tumor microenvironment of MHC-II–expressing cHL, regardless of MHC-I expression status. Consequently, CD4+ T-cell, but not CD8+ T-cell, infiltration was a good prognostic factor in cHL, and PD-1 blockade showed antitumor efficacy against MHC-II–expressing cHL associated with CD4+ T-cell infiltration. Murine lymphoma and solid tumor models revealed the critical role of antitumor effects mediated by CD4+ T cells: an anti-PD-1 monoclonal antibody exerted antitumor effects on MHC-I−MHC-II+ tumors but not on MHC-I−MHC-II− tumors, in a cytotoxic CD4+ T-cell–dependent manner. Furthermore, LAG-3, which reportedly binds to MHC-II, was highly expressed by tumor-infiltrating CD4+ T cells in MHC-II–expressing tumors. Therefore, the combination of LAG-3 blockade with PD-1 blockade showed a far stronger antitumor immunity compared with either treatment alone. We propose that PD-1 blockade therapies have antitumor effects on MHC-II–expressing tumors such as cHL that are mediated by cytotoxic CD4+ T cells and that LAG-3 could be a candidate for combination therapy with PD-1 blockade.

scholarly journals HIV-1 Reservoir Dynamics after Vaccination and Antiretroviral Therapy Interruption Are Associated with Dendritic Cell Vaccine-Induced T Cell Responses

2015 ◽  
Vol 89 (18) ◽  
pp. 9189-9199 ◽  
Author(s):  
Cristina Andrés ◽  
Montserrat Plana ◽  
Alberto C. Guardo ◽  
Carmen Alvarez-Fernández ◽  
Nuria Climent ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Therapeutic Vaccine ◽  
T Cell Responses ◽  
Therapeutic Vaccines ◽  
Cell Responses ◽  
Hiv 1

ABSTRACTHIV-1-specific immune responses induced by a dendritic cell (DC)-based therapeutic vaccine might have some effect on the viral reservoir. Patients on combination antiretroviral therapy (cART) were randomized to receive DCs pulsed with autologous HIV-1 (n= 24) (DC-HIV-1) or nonpulsed DCs (n= 12) (DC-control). We measured the levels of total and integrated HIV-1 DNA in CD4 T cells isolated from these patients at 6 time points: before any cART; before the first cART interruption, which was at 56 weeks before the first immunization to isolate virus for pulsing DCs; before and after vaccinations (VAC1 and VAC2); and at weeks 12 and 48 after the second cART interruption. The vaccinations did not influence HIV-1 DNA levels in vaccinated subjects. After the cART interruption at week 12 postvaccination, while total HIV-1 DNA increased significantly in both arms, integrated HIV-1 DNA did not change in vaccinees (mean of 1.8 log10to 1.9 copies/106CD4 T cells,P= 0.22) and did increase in controls (mean of 1.8 log10to 2.1 copies/106CD4 T cells,P= 0.02) (P= 0.03 for the difference between groups). However, this lack of increase of integrated HIV-1 DNA observed in the DC-HIV-1 group was transient, and at week 48 after cART interruption, no differences were observed between the groups. The HIV-1-specific T cell responses at the VAC2 time point were inversely correlated with the total and integrated HIV-1 DNA levels after cART interruption in vaccinees (r[Pearson's correlation coefficient] = −0.69,P= 0.002, andr= −0.82,P< 0.0001, respectively). No correlations were found in controls. HIV-1-specific T cell immune responses elicited by DC therapeutic vaccines drive changes in HIV-1 DNA after vaccination and cART interruption. (This study has been registered at ClinicalTrials.gov under registration no. NCT00402142.)IMPORTANCEThere is an intense interest in developing strategies to target HIV-1 reservoirs as they create barriers to curing the disease. The development of therapeutic vaccines aimed at enhancing immune-mediated clearance of virus-producing cells is of high priority. Few therapeutic vaccine clinical trials have investigated the role of therapeutic vaccines as a strategy to safely eliminate or control viral reservoirs. We recently reported that a dendritic cell-based therapeutic vaccine was able to significantly decrease the viral set point in vaccinated patients, with a concomitant increase in HIV-1-specific T cell responses. The HIV-1-specific T cell immune responses elicited by this therapeutic dendritic cell vaccine drove changes in the viral reservoir after vaccinations and significantly delayed the replenishment of integrated HIV-1 DNA after cART interruption. These data help in understanding how an immunization could shift the virus-host balance and are instrumental for better design of strategies to reach a functional cure of HIV-1 infection.

Preferential Th2 Polarization at the Onset of Thrombotic Microangiopathy (TMA): Immunological Comparison of TMA Versus Acute GVHD in Terms of Peripheral T Cell Subsets, Dendritic Cell Subsets and Cytokine Profiles.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2885-2885
Author(s):  
Ki-Ryang Koh ◽  
Hirohisa Nakamae ◽  
Kensuke Ohta ◽  
Hideo Koh ◽  
Takahiko Nakane ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Thrombotic Microangiopathy ◽  
Cd4 T Cells ◽  
Acute Gvhd ◽  
T Cell Subsets ◽  
Immunological Parameter ◽  
Hematopoietic Stem ◽  
And Control

Abstract Thrombotic microangiopathy (TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a serious complication with a high mortality. Acute GVHD (aGVHD) is one of risk factors for TMA and often overlaps it. In particular, gastrointestinal endothelium is a common target of aGVHD and TMA, which makes clinical diagnosis of TMA difficult, leading to delay early and appropriate treatment for it. In this study, to gain more insight into differences between TMA and aGVHD, comprehensive immunological analysis was performed. Methods: We determined kinetics of peripheral T cell subsets (CD4, CD8, Th1, Th2, γδ-T, NKT) and dendritic cell (DC) subsets (CD11c+DC and CD123+DC), serum 17 different cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNF-α, IFN-γ, G-CSF, GM-CSF, MIP-1β, MCP-1), and C-reactive protein (CRP) at the onsets of aGVHD or TMA in 25 patients undergoing allo-HSCT. T cell subsets including CD4 (CD3+CD4+CD8−), CD8 (CD3+CD4−CD8+), Th1 (CD4+CXCR3+CCR4−), Th2 (CD4+CXCR3−CCR4+), γδ-T (CD3+TCR-Vδ2+), and NKT (CD3+CD161+) and DC subsets were determined with a flow cytometer. TMA was diagnosed, following Iacopino’s criteria (Iacopino et al, Bone Marrow Tranplant. 24: 47, 1999). Data of aGVHD or TMA were compared with those of control without either aGVHD nor TMA between on 30 days and 60 days after allo-HSCT. Results: There was a significant decrease in the percentage of Th1 cells in CD4+T cells in TMA (9.1%, n=10), compared to in aGVHD (24.9%, n=9, p=0.003) or in control (21.6%, n=12, p=0.009). In contrast, the percentage of Th2 cells in CD4+T cells was higher in TMA (20.2%) than in aGVHD (9.3%, p<0.001) or in control (12.1%, p=0.003). Accordingly, a significant increase in Th2/Th1 ratio was observed in TMA (4.0), compared to in aGVHD (0.4, p<0.001) or in control (0.7, p<0.001). In addition, a significant increase in the percentage of CD4 cells in CD3+T cells in TMA (59.2%, n=9) was found, compared to in aGVHD (31.2%, n=8, p=0.005) or in control (34.8%, n=11, p=0.007). The percentage of CD8+ cells in CD3+T cells was lower in TMA (26.3%) than in aGVHD (45.8%, p=0.03) or in control (54.4%, p=0.002). On the other hand, there was a significant increase in the ratio of CD11c+DC/CD123+DC in aGVHD (3.6, n=8), compared to in TMA (1.4, n=5, p=0.02) or in control (n=1.8, p=0.02). γδ-T and NKT did not show any significant changes among aGVHD, TMA and control. Moreover, no significant changes were observed in either 17 different cytokines among aGVHD, TMA and control. Of note, in TMA but not in aGVHD nor in control, positive correlations of Th2/Th1 ratio were found with IL-6 (p=0.01, r=0.91, n=6), IL-10 (p=0.03, r=0.86, n=6), and CRP (p<0.001, r=0.93, n=9). Conclusion: Preferential Th2 and CD4 polarizations were observed at the onset of TMA. Thus, simultaneous monitoring of Th1, Th2, CD4 and CD8 was suggested to become a useful immunological parameter for differentiating TMA from aGVHD after allo-HSCT.

scholarly journals HIV-1 Nef Enhances Dendritic Cell-Mediated Viral Transmission to CD4+ T Cells and Promotes T-Cell Activation

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e34521 ◽  
Author(s):  
Corine St. Gelais ◽  
Christopher M. Coleman ◽  
Jian-Hua Wang ◽  
Li Wu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Viral Transmission ◽  
Hiv 1

Ex vivo expansion of dendritic-cell-activated antigen-specific CD4+ T cells with anti-CD3/CD28, interleukin-7, and interleukin-15: Potential for adoptive T cell immunotherapy

2006 ◽  
Vol 119 (1) ◽  
pp. 21-31 ◽  
Author(s):  
Hao-Wei Chen ◽  
Cheng-Hao Liao ◽  
Chingwen Ying ◽  
Chun-Jung Chang ◽  
Chun-Ming Lin
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cd4 T Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Interleukin 7 ◽  
Cell Immunotherapy ◽  
Interleukin 15 ◽  
T Cell Immunotherapy

scholarly journals Depletion of Cd4+ T Cells Causes Reactivation of Murine Persistent Tuberculosis despite Continued Expression of Interferon γ and Nitric Oxide Synthase 2

2000 ◽  
Vol 192 (3) ◽  
pp. 347-358 ◽  
Author(s):  
Charles A. Scanga ◽  
V.P. Mohan ◽  
Keming Yu ◽  
Heather Joseph ◽  
Kathryn Tanaka ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
T Cell ◽  
Persistent Infection ◽  
Cd4 T Cells ◽  
Macrophage Activation ◽  
Latent Tuberculosis ◽  
Cd4 T Cell ◽  
Ifn Γ ◽  
Oxide Synthase

Tuberculosis is a major cause of death in much of the world. Current estimates are that one-third of the world's population is infected with Mycobacterium tuberculosis. Most infected persons control the infection but in many cases may not eliminate the organism. Reactivation of this clinically latent infection is responsible for a large proportion of active tuberculosis cases. A major risk factor for reactivation of latent tuberculosis is HIV infection, suggesting a role for the CD4+ T cell subset in maintaining the latent persistent infection. In this study, we tested the requirement for CD4+ T cells in preventing reactivation in a murine model of latent tuberculosis. Antibody-mediated depletion of CD4+ T cells resulted in rapid reactivation of a persistent infection, with dramatically increased bacterial numbers in the organs, increased pathology in the lungs, and decreased survival. Although CD4+ T cells are believed to be a major source of interferon (IFN)-γ, expression of the gene for IFN-γ in the lungs of CD4+ T cell–depleted mice was similar to that in control mice. In addition, inducible nitric oxide synthase production and activity was unimpaired after CD4+ T cell depletion, indicating that macrophage activation was present even during CD4+ T cell deficiency. These data indicate that CD4+ T cells are necessary to prevent reactivation but may have roles in addition to IFN-γ production and macrophage activation in controlling a persistent tuberculous infection.

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