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

1979 ◽  
Vol 31 (1-2) ◽  
pp. 51-63
Author(s):  
A. Massoud ◽  
H. Imanian ◽  
F. Ala
2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5016-5016 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Adam S Kibel ◽  
George Adams ◽  
Lawrence Ivan Karsh ◽  
Aymen Elfiky ◽  
...  

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.


2010 ◽  
Vol 89 (4) ◽  
pp. 526-534 ◽  
Author(s):  
Marina Oliveira Paula ◽  
Denise Morais Fonseca ◽  
Pryscilla Fanini Wowk ◽  
Ana Flávia Gembre ◽  
Paola Fernanda Fedatto ◽  
...  

2020 ◽  
Author(s):  
Lung-Ji Chang ◽  
Cheng-Wei Chang ◽  
Yuchen Liu ◽  
Cheng Jiao ◽  
Hongwei Liu ◽  
...  

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific cellular immune response may prove to be essential for long-term immune protection against the novel coronavirus disease 2019 (COVID-19). To assess COVID-19-specific immunity in the population, we synthesized selected peptide pools of SARS-CoV-2 structural and functional proteins, including Spike (S), Membrane (M), envelope (E), Nucleocapsid (N) and Protease (P) as target antigens. Survey of the T cell precursur frequencies in healthy individuals specific to these viral antigens demonstrated a diverse cellular immunity, including high, medium, low and no responders. This was further confirmed by in vitro induction of anti-SARS-CoV-2 T cell immune responses using dendritic cell (DC)/T cell coculture, which was consistent with the corresponding T cell precursor frequencies in each individual tested. In general, the combination of all five antigenic pools induced the strongest cellular immune response, and individual donors responded differently to different viral antigens. Importantly, a secondary in vitro booster stimulation of the T cells with the DC-peptides induced increased anti-viral immune responses in all individuals even in the no responders, suggesting that booster immunization in a vaccine scheme may elicit a broad protection in immune naïve population. Our analysis illustrates the critical role of cellular immunity in fighting COVID-19 and the importance of analyzing anti-SARS-CoV-2 T cell response in addition to antibody response in the population.


2004 ◽  
Vol 100 (5) ◽  
pp. 1108-1118 ◽  
Author(s):  
Jens A. Kølsen-Petersen ◽  
Jens-Ole D. Nielsen ◽  
Else M. Tonnesen

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.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9070-9070
Author(s):  
Hetty Prinsen ◽  
Jolanda de Vries ◽  
Foekje Stelma ◽  
Sasja Mulder ◽  
Carla Van Herpen ◽  
...  

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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