Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro

Science ◽  
1993 ◽  
Vol 262 (5140) ◽  
pp. 1721-1724 ◽  
Author(s):  
M Clerici ◽  
D. Lucey ◽  
J. Berzofsky ◽  
L. Pinto ◽  
T. Wynn ◽  
...  
Keyword(s):  
Immune Responses ◽  
Interleukin 12 ◽  
Specific Cell

scholarly journals Bartonella henselae-Specific Cell-Mediated Immune Responses Display a Predominantly Th1 Phenotype in Experimentally Infected C57BL/6 Mice

2001 ◽  
Vol 69 (10) ◽  
pp. 6427-6433 ◽  
Author(s):  
Mardjan Arvand ◽  
Ralf Ignatius ◽  
Thomas Regnath ◽  
Helmut Hahn ◽  
Martin E. A. Mielke
Keyword(s):  
Immune Responses ◽  
Bartonella Henselae ◽  
Interleukin 4 ◽  
Infection Model ◽  
Antibody Concentration ◽  
Specific Cell ◽  
Spleen Cells ◽  
Viable Bacteria ◽  
Igg Isotypes

ABSTRACT Immune responses of the immunocompetent host to Bartonella henselae infection were investigated in the murine infection model using C57BL/6 mice. Following intraperitoneal infection with human-derived B. henselae strain Berlin-1, viable bacteria could be recovered from livers and spleens during the first week postinfection, while Bartonella DNA remained detectable by PCR in the liver for up to 12 weeks after infection. Granulomatous lesions developed in livers of infected mice, reached maximal density at 12 weeks after infection, and persisted for up to 20 weeks, indicating that B. henselae induced a chronic granulomatous hepatitis in the immunocompetent murine host. T-cell-mediated immune responses were analyzed in vitro by means of spleen cell proliferation and cytokine release assays as well as analysis of immunoglobulin G (IgG) isotypes. Spleen cells from infected mice proliferated specifically upon stimulation with heat-killedBartonella antigen. Proliferative responses were mainly mediated by CD4+ T cells, increased during the course of infection, peaked at 8 weeks postinfection, and decreased thereafter. Gamma interferon, but not interleukin-4, was produced in vitro by spleen cells from infected animals upon stimulation withBartonella antigens. Bartonella-specific IgG was detectable in serum of infected mice by 2 weeks, and the antibody concentration peaked at 12 weeks postinfection. IgG2b was the prominent isotype among the Bartonella-specific serum IgG antibodies. These data indicate that B. henselaeinduces cell-mediated immune responses with a Th1 phenotype in immunocompetent C57BL/6 mice.

In vitro measurement of antigen-specific cell-mediated immune responses using recombinant HIV-1 proteins adsorbed to latex microspheres

1991 ◽  
Vol 143 (1) ◽  
pp. 1-9 ◽  
Author(s):  
J.-Y. Wu ◽  
C.H. Riggin ◽  
J.R. Seals ◽  
C.I. Murphy ◽  
M.J. Newman
Keyword(s):  
Immune Responses ◽  
Specific Cell ◽  
Hiv 1

scholarly journals Stimulation of Dendritic Cells via CD40 Enhances Immune Responses to Mycobacterium tuberculosisInfection

2001 ◽  
Vol 69 (4) ◽  
pp. 2456-2461 ◽  
Author(s):  
Caroline Demangel ◽  
Umaimainthan Palendira ◽  
Carl G. Feng ◽  
Andrew W. Heath ◽  
Andrew G. D. Bean ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Interleukin 12 ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Stimulation Of

ABSTRACT The resolution of pulmonary tuberculosis (TB) critically depends on the development of the Th1 type of immune responses, as exemplified by the exacerbation of TB in IL-12-deficient mice. Therefore, vaccination strategies optimizing IL-12 production by antigen-presenting cells (APC) in response to mycobacteria may have enhanced protective efficacy. Since dendritic cells (DC) are the critical APC for activation of CD4+ and CD8+ T cells, we examined whether stimulation of Mycobacterium bovis bacillus Calmette Guérin (BCG)-infected DC via CD40 increased their ability to generate Th1-oriented cellular immune responses. Incubation of DC with an agonistic anti-CD40 antibody activated CD40 signaling in DC, as shown by increased expression of major histocompatibility complex class II and costimulatory molecules, mRNA production for proinflammatory cytokines and interleukin 12 (IL-12) p40. This activation pattern was maintained when DC were stimulated with anti-CD40 antibody and infected with BCG. Importantly, CD40-stimulated BCG-infected DC displayed increased capacity to release bioactive IL-12 and to activate gamma interferon (IFN-γ) producing T cells in vitro. Moreover, when C57BL/6 mice were immunized with these DC and challenged with aerosol Mycobacterium tuberculosis, increased levels of mRNA for IL-12 p40, IL-18, and IFN-γ were present in the draining mediastinal lymph nodes. However, the mycobacterial burden in the lungs was not reduced compared to that in mice immunized with BCG-infected non-CD40-stimulated DC. Therefore, although the manipulation of DC via CD40 is effective for enhancing immune responses to mycobacteria in vivo, additional strategies are required to increase protection against virulent M. tuberculosis infection.

scholarly journals Incorporation of CD40 Ligand into the Envelope of Pseudotyped Single-Cycle Simian Immunodeficiency Viruses Enhances Immunogenicity

2008 ◽  
Vol 83 (3) ◽  
pp. 1216-1227 ◽  
Author(s):  
Fan-ching Lin ◽  
Yue Peng ◽  
Leslie A. Jones ◽  
Paulo H. Verardi ◽  
Tilahun D. Yilma
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd40 Ligand ◽  
Interleukin 12 ◽  
Vaccine Strategy ◽  
Aids Vaccine ◽  
Cytokines And Chemokines ◽  
Hla Dr ◽  
Aids Pandemic

ABSTRACT A vaccine for the prevention of human immunodeficiency virus (HIV) infection is desperately needed to control the AIDS pandemic. To address this problem, we developed vesicular stomatitis virus glycoprotein-pseudotyped replication-defective simian immunodeficiency viruses (dSIVs) as an AIDS vaccine strategy. The dSIVs retain characteristics of a live attenuated virus without the drawbacks of potential virulence caused by replicating virus. To improve vaccine immunogenicity, we incorporated CD40 ligand (CD40L) into the dSIV envelope. CD40L is one of the most potent stimuli for dendritic cell (DC) maturation and activation. Binding of CD40L to its receptor upregulates expression of major histocompatibility complex class I, class II, and costimulatory molecules on DCs and increases production of proinflammatory cytokines and chemokines, especially interleukin 12 (IL-12). This cytokine polarizes CD4+ T cells to Th1-type immune responses. DC activation and mixed lymphocyte reaction (MLR) studies were performed to evaluate the immunogenicity of CD40L-dSIV in vitro. Expression levels of CD80, CD86, HLA-DR, and CD54 on DCs transduced with the dSIV incorporating CD40L (CD40L-dSIV) were significantly higher than on those transduced with dSIV. Moreover, CD40L-dSIV-transduced DCs expressed up to 10-fold more IL-12 than dSIV-transduced DCs. CD40L-dSIV-transduced DCs enhanced proliferation and gamma interferon secretion by naive T cells in an MLR. In addition, CD40L-dSIV-immunized mice exhibited stronger humoral and cell-mediated immune responses than dSIV-vaccinated animals. The results show that incorporating CD40L into the dSIV envelope significantly enhances immunogenicity. As a result, CD40L-dSIVs can be strong candidates for development of a safe and highly immunogenic AIDS vaccine.

scholarly journals The Selenoprotein MsrB1 Instructs Dendritic Cells to Induce T-Helper 1 Immune Responses

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1021
Author(s):  
Ho-Jae Lee ◽  
Joon Seok Park ◽  
Hyun Jung Yoo ◽  
Hae Min Lee ◽  
Byung Cheon Lee ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Methionine Sulfoxide Reductase ◽  
Interleukin 12 ◽  
T Helper ◽  
T Helper 1

Immune activation associates with the intracellular generation of reactive oxygen species (ROS). To elicit effective immune responses, ROS levels must be balanced. Emerging evidence shows that ROS-mediated signal transduction can be regulated by selenoproteins such as methionine sulfoxide reductase B1 (MsrB1). However, how the selenoprotein shapes immunity remains poorly understood. Here, we demonstrated that MsrB1 plays a crucial role in the ability of dendritic cells (DCs) to provide the antigen presentation and costimulation that are needed for cluster of differentiation antigen four (CD4) T-cell priming in mice. We found that MsrB1 regulated signal transducer and activator of transcription-6 (STAT6) phosphorylation in DCs. Moreover, both in vitro and in vivo, MsrB1 potentiated the lipopolysaccharide (LPS)-induced Interleukin-12 (IL-12) production by DCs and drove T-helper 1 (Th1) differentiation after immunization. We propose that MsrB1 activates the STAT6 pathway in DCs, thereby inducing the DC maturation and IL-12 production that promotes Th1 differentiation. Additionally, we showed that MsrB1 promoted follicular helper T-cell (Tfh) differentiation when mice were immunized with sheep red blood cells. This study unveils as yet unappreciated roles of the MsrB1 selenoprotein in the innate control of adaptive immunity. Targeting MsrB1 may have therapeutic potential in terms of controlling immune reactions.

scholarly journals Dialyzable Leukocyte Extracts Activate TLR-2 on Monocytes

2014 ◽  
Vol 9 (6) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Uriel García-Hernández ◽  
Frank H. Robledo-Ávila ◽  
Violeta D. Álvarez-Jiménez ◽  
Octavio Rodríguez-Cortés ◽  
Isabel Wong-Baeza ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Specific Cell ◽  
Toll Like Receptor ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Activated Monocytes

Dialyzable leukocyte extracts (DLE) transfer specific cell-mediated immune responses from sensitized donors to non-immune recipients. In addition, DLE have several immunomodulatory effects and are used for the treatment of several infectious and non-infectious diseases. Previous studies showed that human DLE obtained from virus-infected leukocytes and bovine DLE decrease the production of the pro-inflammatory cytokine TNF-α in response to bacterial lipopolysaccharide, in vitro and in vivo. In the present work, we inquire as to whether DLE from uninfected human leukocytes have the ability to regulate cytokine production in peripheral blood mononuclear cells (PBMC) in vitro. We observed that PBMC from healthy individuals were able to produce TNF-α, IL-12 and IL-10 after stimulation with DLE. Moreover, we identified monocytes as the main cell population that produced TNF-α after DLE stimulation. Interestingly, we found that DLE contain unidentified ligands that activate Toll-like receptor (TLR)-2. Finally, we observed that DLE directly activated monocytes through TLR-2. These results reveal a new biological activity of DLE, and suggest that part of the immunomodulatory properties of DLE could be attributed to TLR-2 activation on monocytes and to the induction of a pro-inflammatory environment that is crucial for control of infectious diseases.

scholarly journals Induction of Antigen-Specific Th1-Type Immune Responses by Gamma-Irradiated Recombinant Brucella abortus RB51

2005 ◽  
Vol 12 (12) ◽  
pp. 1429-1436 ◽  
Author(s):  
Neelima Sanakkayala ◽  
Anna Sokolovska ◽  
Jatinder Gulani ◽  
Harm HogenEsch ◽  
Nammalwar Sriranganathan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Gamma Radiation ◽  
Brucella Abortus ◽  
The United States ◽  
Interleukin 12 ◽  
Heterologous Proteins ◽  
Heterologous Antigen ◽  
Gamma Irradiated ◽  
Th1 Immune Responses

ABSTRACT Brucella abortus strain RB51 is an attenuated rough mutant used as the live vaccine against bovine brucellosis in the United States and other countries. We previously reported the development of strain RB51 as a bacterial vaccine vector for inducing Th1-type immune responses against heterologous proteins. Because safety concerns may preclude the use of strain RB51-based recombinant live vaccines, we explored the ability of a gamma-irradiated recombinant RB51 strain to induce heterologous antigen-specific immune responses in BALB/c mice. Exposure of strain RB51G/LacZ expressing Escherichia coli β-galactosidase to a minimum of 300 kilorads of gamma radiation resulted in complete loss of replicative ability. These bacteria, however, remained metabolically active and continued to synthesize β-galactosidase. A single intraperitoneal inoculation of mice with 109 CFU equivalents of gamma-irradiated, but not heat-killed, RB51G/LacZ induced a β-galactosidase-specific Th1-type immune response. Though no obvious differences were detected in immune responses to B. abortus-specific antigens, mice vaccinated with gamma-irradiated, but not heat-killed, RB51G/LacZ developed significant protection against challenge with virulent B. abortus. In vitro experiments indicated that gamma-irradiated and heat-killed RB51G/LacZ induced maturation of dendritic cells; however, stimulation with gamma-irradiated bacteria resulted in more interleukin-12 secretion. These results suggest that recombinant RB51 strains exposed to an appropriate minimum dose of gamma radiation are unable to replicate but retain their ability to stimulate Th1 immune responses against the heterologous antigens and confer protection against B. abortus challenge in mice.

scholarly journals Local Anticandidal Immune Responses in a Rat Model of Vaginal Infection by and Protection against Candida albicans

2000 ◽  
Vol 68 (6) ◽  
pp. 3297-3304 ◽  
Author(s):  
Flavia de Bernardis ◽  
Giorgio Santoni ◽  
Maria Boccanera ◽  
Elisabetta Spreghini ◽  
Daniela Adriani ◽  
...  
Keyword(s):  
T Cells ◽  
Candida Albicans ◽  
T Cell ◽  
Immune Responses ◽  
Interleukin 2 ◽  
Interleukin 12 ◽  
Vaginal Fluid ◽  
In Vitro Proliferation ◽  
The Third

ABSTRACT Humoral (antibody [Ab]) and cellular Candida-specific immune responses in the vaginas of pseudoestrus rats were investigated during three successive infections by Candida albicans. After the first, protective infection, Abs against mannan and aspartyl proteinase antigens were present in the vaginal fluid, and their titers clearly increased during the two subsequent, rapidly healing infections. In all animals, about 65 and 10% of vaginal lymphocytes (VL) were CD3+ (T cells) and CD3−CD5+ (B cells), respectively. Two-thirds of the CD3+ T cells expressed the α/β and one-third expressed the γ/δ T-cell receptor (TCR). This proportion slightly fluctuated during the three rounds of C. albicans infection, but no significant differences between infected and noninfected rats were found. More relevant were the changes in the CD4+/CD8+ T-cell ratio, particularly for cells bearing the CD25 (interleukin-2 receptor α) marker. In fact, a progressively increased number of both CD4+ α/β TCR and CD4+ CD25+ VL was observed after the second and third Candida challenges, reversing the high initial CD8+ cell number of controls (estrogenized but uninfected rats). The CD3− CD5+ cells also almost doubled from the first to the third infection. Analysis of the cytokines secreted in the vaginal fluid of Candida-infected rats showed high levels of interleukin 12 (IL-12) during the first infection, followed by progressively increasing amounts of IL-2 and gamma interferon during the subsequent infections. No IL-4 or IL-5 was ever detected. During the third infection, VL with in vitro proliferative activity in response to an immunodominant mannoprotein antigen of C. albicans were present in the vaginal tissue. No response to this antigen by mitogen-responsive blood, lymph node, and spleen cells was found. In summary, the presence of protective Ab and T helper type 1 cytokines in the vaginal fluids, the in vitro proliferation of vaginal lymphocytes in response toCandida antigenic stimulation, and the increased number of activated CD4+ cells and some special B lymphocytes afterC. albicans challenge constitute good evidence for induction of locally expressed Candida-specific Ab and cellular responses which are potentially involved in anticandidal protection at the vaginal level.

scholarly journals Identification of an HLA-A*0201–restricted CD8+ T-cell epitope SSp-1 of SARS-CoV spike protein

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 200-206 ◽  
Author(s):  
Baomei Wang ◽  
Huabiao Chen ◽  
Xiaodong Jiang ◽  
Minghui Zhang ◽  
Tao Wan ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Immune Responses ◽  
Cell Epitope ◽  
Specific Cell ◽  
Control Mechanisms ◽  
S Protein ◽  
Specific Ctls ◽  
Hla A2.1

Abstract A novel coronavirus, severe acute respiratory syndrome (SARS)–associated coronavirus (SARS-CoV), has been identified as the causal agent of SARS. Spike (S) protein is a major structural glycoprotein of the SARS virus and a potential target for SARS-specific cell-mediated immune responses. A panel of S protein–derived peptides was tested for their binding affinity to HLA-A*0201 molecules. Peptides with high affinity for HLA-A*0201 were then assessed for their capacity to elicit specific immune responses mediated by cytotoxic T lymphocytes (CTLs) both in vivo, in HLA-A2.1/Kb transgenic mice, and in vitro, from peripheral blood lymphocytes (PBLs) sourced from healthy HLA-A2.1+ donors. SARS-CoV protein-derived peptide-1 (SSp-1 RLNEVAKNL), induced peptide-specific CTLs both in vivo (transgenic mice) and in vitro (human PBLs), which specifically released interferon-γ (IFN-γ) upon stimulation with SSp-1–pulsed autologous dendritic cells (DCs) or T2 cells. SSp-1–specific CTLs also lysed major histocompatibility complex (MHC)–matched tumor cell lines engineered to express S proteins. HLA-A*0201–SSp-1 tetramer staining revealed the presence of significant populations of SSp-1–specific CTLs in SSp-1–induced CD8+ T cells. We propose that the newly identified epitope SSp-1 will help in the characterization of virus control mechanisms and immunopathology in SARS-CoV infection, and may be relevant to the development of immunotherapeutic approaches for SARS.

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