Host genetic background affects regulatory T‐cell activity that influences the magnitude of cellular immune response against
            Mycobacterium tuberculosis

5016 Background: ADT is a standard treatment for men with BRPC after failure of local therapy, and has immunomodulatory effects. Sipuleucel-T is an autologous cellular immunotherapy approved for asymptomatic/minimally symptomatic metastatic castrate resistant prostate cancer. The STAND trial (NCT01431391) aimed to evaluate optimal sequencing of sipuleucel-T and ADT in men with BRPC at high risk for metastases (ie PSA doubling time ≤12 mo). Methods: Men were randomized (1:1) to Arm 1: sipuleucel-T followed by ADT (2 wks after 3rd infusion); or Arm 2: ADT (3 mo lead in) followed by sipuleucel-T. All men had 3 doses of sipuleucel-T and 12 mo of ADT (45 mg leuprolide SQ at 6 mo intervals). The primary endpoint is cellular immune response (ELISPOT to PA2024 [PAP-GMCSF]). Secondary endpoints are humoral and cytokine responses, product parameters and safety. Results: 68 men were randomized. Preliminary data show higher levels of serum cytokines in Arm 2 vs Arm 1, with a pattern suggesting a mixed TH1/TH2 cellular immune response; elevations were seen in TH1 (IFNγ, IL 12), TH2 (IL 4, 5, 10, 13) and TH17 (IL 17) subsets (all P<.05). The increase in TH1 cytokines was consistent with a trend toward higher PA2024-specific ELISPOT responses 2 wk after the 3rd sipuleucel-T infusion in Arm 2 vs Arm 1 (40.5 vs 12.8 spots; P=.086), suggesting increased T cell activation in Arm 2. Antigen-specific humoral responses were induced in both arms with no differences yet observed between arms. Sipuleucel-T product parameters were roughly equivalent in both arms with APC activation data indicating a robust prime-boost effect. Conclusions: While confirmation is required, these preliminary data suggest that tumor-specific T cell responses and broad based immune responses are augmented when sipuleucel-T is given after rather than before ADT initiation. These data are consistent with preclinical studies showing that ADT enhances T cell activity, and provide preliminary evidence that combining ADT with sipuleucel-T may augment adaptive immunity. Further follow up will determine whether augmented immune responses correlate with clinical parameters (eg PSA recurrence). Clinical trial information: NCT01431391.

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Mitogen-induced suppressor T cell activity in the in vitro cellular immune response

Journal of Immunological Methods ◽

10.1016/0022-1759(79)90285-0 ◽

1979 ◽

Vol 31 (1-2) ◽

pp. 51-63

Author(s):

A. Massoud ◽

H. Imanian ◽

F. Ala

Keyword(s):

Immune Response ◽

T Cell ◽

Cellular Immune Response ◽

Cell Activity ◽

Suppressor T Cell ◽

Cellular Immune

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Effect of Hypertonic Saline Infusion on Postoperative Cellular Immune Function

Anesthesiology ◽

10.1097/00000542-200405000-00012 ◽

2004 ◽

Vol 100 (5) ◽

pp. 1108-1118 ◽

Cited By ~ 15

Author(s):

Jens A. Kølsen-Petersen ◽

Jens-Ole D. Nielsen ◽

Else M. Tonnesen

Keyword(s):

Immune Response ◽

Immune Function ◽

Hypertonic Saline ◽

Cellular Immune Response ◽

Killer Cell ◽

Cell Activity ◽

Abdominal Hysterectomy ◽

Delayed Type Hypersensitivity ◽

Laboratory Animals ◽

Cellular Immune

Background Previous studies found hypertonicity to affect immune responses in intact laboratory animals and in human blood cell cultures. In this study, the authors investigated the cellular immune response to surgery after preoperative infusion of hypertonic saline in humans. Methods Sixty-two women scheduled to undergo abdominal hysterectomy were randomly assigned to single-blinded infusion of 4 ml/kg NaCl, 7.5%; 4 ml/kg NaCl, 0.9%; or 32 ml/kg NaCl, 0.9%, over 20 min. Blood was collected at baseline, during surgery, and 1, 24, and 48 h after surgery for the determination of leukocyte and differential counts, flow cytometric phenotyping of mononuclear cells, and natural killer cell activity against K 562 tumor cells. Phytohemagglutinin-induced lymphocyte proliferation, plasma elastase, and neutrophil chemotaxis were measured at the same time points except during surgery. The authors tested cell-mediated immune function in vivo by delayed-type hypersensitivity reaction in the skin. Results Surgery induced well-known changes in the cellular immune response, which were unrelated to the tonicity or volume of the infused fluids. Conclusion Infusion of a clinically relevant dose of hypertonic saline did not seem to modify the postoperative cellular immune response after elective abdominal hysterectomy.

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Humoral and cellular immune response after influenza vaccination in patients with postcancer fatigue and patients with chronic fatigue syndrome.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9070 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9070-9070

Author(s):

Hetty Prinsen ◽

Jolanda de Vries ◽

Foekje Stelma ◽

Sasja Mulder ◽

Carla Van Herpen ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Chronic Fatigue Syndrome ◽

Cellular Immune Response ◽

Foxp3 Expression ◽

Chronic Fatigue ◽

Fatigue Syndrome ◽

Patient Groups ◽

Postcancer Fatigue ◽

Cellular Immune

9070 Background: Postcancer fatigue (PCF) is a frequently occurring problem, impairing quality of life. Patients with chronic fatigue syndrome (CFS) also suffer from severe fatigue symptoms. We hypothesized that in fatigued patients (PCF and CFS) alterations in immune response could explain fatigue symptoms. Therefore, we examined whether the humoral and/or cellular immune response after influenza vaccination differed between fatigued patients and non-fatigued individuals and between PCF and CFS patients. Methods: PCF (n=15) and CFS patients (n=22) were vaccinated against influenza. Age and gender matched non-fatigued cancer survivors (n=12) and healthy controls (n=23) were included for comparison. Antibody responses were measured at baseline and at day 21 by a hemagglutination inhibition test. T cell responses were measured at baseline and at day 7 by a lymphocyte proliferation and activation assay. Results: Both patient groups developed seroprotection rates comparable to the accompanying control groups. Functional T cell reactivity was observed in all groups. Proliferation at baseline was significantly lower in fatigued patients compared to non-fatigued individuals. A significant increase in proliferation from baseline to day 7 was observed in fatigued patients, but not in controls. At day 7, proliferation was not significantly different between fatigued patients and non-fatigued individuals. CD4+CD127-FoxP3+ expression was significantly higher in PCF patients compared to non-fatigued cancer survivors. Conclusions: We observed a lower T cell proliferation at baseline in fatigued patients compared to non-fatigued individuals, suggesting a difference in the baseline state of the immune system between fatigued patients and non-fatigued individuals. Furthermore, the difference in CD4+CD127-FoxP3+ expression between PCF and CFS patients suggests subtle differences in immune state between these two fatigued patient groups. However, since humoral and cellular immune responses after vaccination did not differ significantly between fatigued patients and non-fatigued individuals, vaccination of fatigued patients (PCF and CFS) can be effective.

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Humoral and Cellular Immune Response to RNA Immunization with Flavivirus Replicons Derived from Tick-Borne Encephalitis Virus

Journal of Virology ◽

10.1128/jvi.79.24.15107-15113.2005 ◽

2005 ◽

Vol 79 (24) ◽

pp. 15107-15113 ◽

Cited By ~ 45

Author(s):

Judith H. Aberle ◽

Stephan W. Aberle ◽

Regina M. Kofler ◽

Christian W. Mandl

Keyword(s):

Immune Response ◽

T Cell ◽

Cell Response ◽

Cellular Immune Response ◽

T Cell Response ◽

The Self ◽

Tick Borne Encephalitis ◽

Tick Borne Encephalitis Virus ◽

Cellular Immune ◽

Rna Vaccine

ABSTRACT A new vaccination principle against flaviviruses, based on a tick-borne encephalitis virus (TBEV) self-replicating noninfectious RNA vaccine that produces subviral particles, has recently been introduced (R. M. Kofler, J. H. Aberle, S. W. Aberle, S. L. Allison, F. X. Heinz, and C. W. Mandl, Proc. Natl. Acad. Sci. USA 7:1951-1956, 2004). In this study, we evaluated the potential of the self-replicating RNA vaccine in mice in comparison to those of live, attenuated vaccines and a formalin-inactivated whole-virus vaccine (ImmunInject). For this purpose, mice were immunized using gene gun-mediated application of the RNA vaccine and tested for CD8+ T-cell responses, long-term duration, neutralizing capacity, and isotype profile of specific antibodies and protection against lethal virus challenge. We demonstrate that the self-replicating RNA vaccine induced a broad-based, humoral and cellular (Th1 and CD8+ T-cell response) immune response comparable to that induced by live vaccines and that it protected mice from challenge. Even a single immunization with 1 μg of the replicon induced a long-lasting antibody response, characterized by high neutralizing antibody titers, which were sustained for at least 1 year. Nevertheless, it was possible to boost this response further by a second injection with the RNA vaccine, even in the presence of a concomitant CD8+ T-cell response. In this way it was possible to induce a balanced humoral and cellular immune response, similar to infection-induced immunity but without the safety hazards of infectious agents. The results also demonstrate the value of TBEV replicon RNA for inducing protective long-lasting antiviral responses.

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Immunomodulatory effects ofPteridium aquilinumon natural killer cell activity and select aspects of the cellular immune response of mice

Journal of Immunotoxicology ◽

10.1080/15476910902972465 ◽

2009 ◽

Vol 6 (2) ◽

pp. 104-114 ◽

Cited By ~ 20

Author(s):

Andréia Oliveira Latorre ◽

Maria Stella Furlan ◽

Mônica Sakai ◽

Heidge Fukumasu ◽

Isis Machado Hueza ◽

...

Keyword(s):

Immune Response ◽

Natural Killer Cell ◽

Natural Killer ◽

Cellular Immune Response ◽

Natural Killer Cell Activity ◽

Killer Cell ◽

Cell Activity ◽

Immunomodulatory Effects ◽

Killer Cell Activity ◽

Cellular Immune

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Endogenous Il10 Alleviates the Systemic Antiviral Cellular Immune Response and T Cell–Mediated Immunopathology in Select Organs of Acutely LCMV-Infected Mice

American Journal Of Pathology ◽

10.1016/j.ajpath.2015.07.019 ◽

2015 ◽

Vol 185 (11) ◽

pp. 3025-3038 ◽

Cited By ~ 3

Author(s):

Kristin Jakobshagen ◽

Beate Ward ◽

Nikola Baschuk ◽

Sebastian Huss ◽

Anna Brunn ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Cellular Immune Response ◽

Cellular Immune

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Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

Vaccines ◽

10.3390/vaccines9111273 ◽

2021 ◽

Vol 9 (11) ◽

pp. 1273

Author(s):

Kirill Vasilyev ◽

Anna-Polina Shurygina ◽

Natalia Zabolotnykh ◽

Mariia Sergeeva ◽

Ekaterina Romanovskaya-Romanko ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Cellular Immune Response ◽

Vaccine Candidate ◽

Protective Efficacy ◽

Adaptive Immune Response ◽

Reading Frame ◽

Vector Vaccine ◽

Specific Effector ◽

Cellular Immune

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

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Complementary Presence of HBV-Specific Humoral and T-Cellular Immune Response Provide the Long-Lasting Immune Protection After Neonatal Immunization

10.21203/rs.3.rs-436535/v1 ◽

2021 ◽

Author(s):

Yunmei Huang ◽

Yuting Yang ◽

Tingting Wu ◽

Zhiyu Li ◽

Yao Zhao

Keyword(s):

Immune Response ◽

T Cell ◽

Hepatitis B ◽

Cell Response ◽

Cellular Immune Response ◽

Cellular Response ◽

T Cell Response ◽

Hbv Infection ◽

Hepatitis B Vaccination ◽

Cellular Immune

Abstract Background: Hepatitis B vaccination is the most cost-effective way to prevent HBV infection. Currently, hepatitis B vaccine (HepB) efficacy was usually assessed by anti-HBs level, but there were little comprehensive analyses of humoral and cellular immune response to HepB in children after neonatal immunization. Methods: A total of 145 children with primary hepatitis B immunization history were involved in this study to evaluate the efficacy of HepB. Blood samples were obtained from 80 eligible children before one dose of HepB booster and 41 children post-booster. Children with anti-HBs at a low level (<10mIU/mL and [10,100) mIU/mL) were received one dose of HepB booster after informed consent. Subjects were be measured anti-HBs, HBsAg-specific T cell responses and frequency of B cell subsets before and after booster. Results: Among 80 subjects, 81.36% of children showed both T cell and anti-HBs responses positive at baseline. After one dose of booster, anti-HBs titer (P<0.0001), positive rate of HBsAg-specific T cell response (P=0.0036) and magnitude of SFCs (P=0.0003) increased significantly. Comparing preexisting anti-HBs titer <10mIU/mL with anti-HBs titer [10,100) mIU/mL, anti-HBs response (P=0.0005) and HBsAg-specific T lymphocyte response (P<0.0001) increased significantly. The change tendency of HBV specific humoral response is complementary to T cellular response with age. Conclusion: Protection from primary HBV immunization persists long on account of the complementary presence of HBV-specific humoral and T-cellular immune response. One dose of HepB booster is efficient enough to produce protective anti-HBs and enhance HBsAg-specific T cell response. In the HBV endemic areas, HepB booster immunization is still the most economical and effective way to prevent HBV infection, especially in children without anti-HBs.

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