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Background: An acute respiratory distress syndrome (ARDS) is caused by the increased amounts of pro-inflammatory cytokines and neutrophil-mediated tissue injury. To date, there is no effective treatment for the ARDS available, while the need for one is growing due to the most severe complications of the current coronavirus disease-2019 (COVID-19) pandemic. The human astrocytes (AstroRx) have shown immunomodulatory properties in the central nervous system (CNS). This study aimed to evaluate the capacity of astrocytes to decrease lung inflammation and to be applied as a treatment therapy in ARDS.Methods: First, we assessed the ability of clinical-grade AstroRx to suppress T-cell proliferation in a mixed lymphocyte reaction test. Next, we tested the therapeutical potential of AstroRx cells in a lipopolysaccharide (LPS)-based ARDS mouse model by injecting AstroRx intravenously (i.v). We determined the degree of lung injury by using a severity scoring scale of 0–2, based on the American Thoracic Society. The scoring measured the presence of neutrophils, fibrin deposits, and the thickening of alveolar walls. The state of inflammation was further assessed by quantifying the immune-cell infiltration to the bronchoalveolar lavage fluid (BALF) and by the presence of proinflammatory cytokines and chemokines in the BALF and serum.Results: We detected that AstroRx cells were capable to suppress T-cell proliferation in vitro after exposure to the mitogen concanavalin A (ConA). In vivo, AstroRx cells were able to lower the degree of lung injury in LPS-treated animals compared with the sham injected animals (P = 0.039). In this study, 30% of AstroRx treated mice showed no lung lesions (responder mice), these mice presented a steady number of eosinophils, T cells, and neutrophils comparable with the level of naïve control mice. The inflammatory cytokines and chemokines, such as TNFα, IL1b, IL-6, and CXCL1, were also kept in check in responder AstroRx-treated mice and were not upregulated as in the sham-injected mice (P < 0.05). As a result, the LPS-treated ARDS mice had a higher survival rate when they were treated with AstroRx.Conclusions: Our results demonstrate that the immunosuppressive activity of AstroRx cells support the application of AstroRx cells as a cell therapy treatment for ARDS. The immunoregulatory activity may also be a part of the mechanism of action of AstroRx reported in the amyotrophic lateral sclerosis (ALS) neurodegenerative disease.

Earlier studies noted that patients who underwent cord blood (CB) transplantation had a lower incidence of graft-versus-host disease (GVHD) than those who underwent bone marrow transplantation (BMT). The premise that the immune reactivity of CB mononuclear cells (CB-MNC) to HLA mismatched combinations and to noninherited maternal antigens (NIMA) may be one of the factors involved in this phenomenon is still debatable. In this study we have attempted to evaluate the alloresponse and alloreactivity induced by CB-MNC by means of the standard mixed lymphocyte reaction test (SMLR) and the more sensitive, modified mixed lymphocyte reaction test (MMLR). Both techniques were used to test CB-MNC ( n = 28) against HLA class II mismatched MNC from mothers ( n = 26), fathers ( n = 12), and unrelated individuals ( n = 60) who served as controls. Alloresponse capabilities and stimulation capacities of CB-MNC in the SMLR were similar to those of control MNC: relative response (RR) = 73 vs. 65 and 58 vs. 65, respectively. Similar results were obtained in the MMLR. CB-MNC responded weakly to the maternal MNC in comparison with control MNC (RR = 47 vs. 73 [ p = 0.0099]), while a stronger response was noted to the paternal than the maternal MNC (RR = 72 vs. 47 [ p = 0.045]). Our results demonstrate that CB-MNC both respond to and induce alloresponse in HLA mismatched combinations. Moreover, the hyporesponse of CB-MNC to maternal cells that we observed suggests a form of tolerance to NIMA, which is probably due to the fetus’s exposure to these antigens in its intrauterine life.

Immunomodulatory activities of aqueous and protein extracts of Berberis hispanica were evaluated in vitro. Both extracts at 1 mg/ml showed no cytotoxicity effect on thymocytes, splenocytes and macrophages cells. These extracts strongly inhibited in vitro the mitogen proliferative response of thymocyte and spleen cells. Humoral immunity measured by plaque-forming cell assay and evolution of complement activity showed an increase of plaque-forming cell formed and complement activity after addition of protein extract, where aqueous extract induced a significant diminution only in plaque-forming cell. In addition, the same extracts elicited a significant decrease in phagocytic capacity without affecting macrophage cells viability. In the allogenic mixed lymphocyte reaction test, plant extracts mainly increased lymphocyte cytotoxic activity towards chicken red bloods cells. The present data support that Berberis hispanica extracts showed an immunosuppressive action on proliferation and biological effects of T-cell and B-cell. This suggests a possible use of aqueous extract in auto-immune diseases therapy. However, the protein extract, highly stimulates allogenic mixed lymphocyte which suggest an interesting use in cancer therapy. Key words: Berberis hispanica, immunomodulation, plaque-forming cell, allogenic mixed lymphocyte phagocytosis.

Twenty years after the Chernobyl accident, 137-Caesium (137-Cs) is the main residual radionuclide found in contaminated areas. 137-Cs progressively integrated food chains until man, inducing a chronic contamination of large populations through daily ingestion of small quantities of 137-Cs. Some studies indicated an accumulation of 137-Cs in the thyroid, the heart and muscles. It was then suggested that 137-Cs contamination could lead to some pathologies observed within populations living onto contaminated areas. In order to determine the possible influence of Cs137 onto the immune system, we developed a mouse model of chronic contamination through drinking water with a concentration of 20 KBq.l-1 of 137-Cs. This corresponds to a daily ingestion of 6 KBq.day-1.kg of body weight, ten times higher than the highest measurements made after the Chernobyl accident. Parent animals were contaminated before mating and during gestation. After weaning, contamination of offspring was continued through drinking water. Gamma counts indicated that 137-Cs was found in all tissue tested at a concentration between 2 and 20 Bq/g of tissue. However, a progressive accumulation of 137-Cs was observed in muscles and kidney, and to a lesser extend in the heart and in femurs, mainly until 9 weeks of age. The immune system was evaluated by several means, including phenotypic and functional analyses. Phenotypic analysis of blood cells did not showed significant changes in both CD4+ and CD8+ T lymphocytes, in CD4+CD25+ Tregs, or in B220+ B lymphocytes between control and 137-Cs contaminated animals. Intrathymic differentiation was evaluated by phenotypic analysis of thymocyte subpopulation and by T cell excision circle (Trec) detection. However, no significant changes in intra-thymic differentiation were observed whatever the age of animals. Three functional tests were also used to evaluate the immune system, response of splenocytes to a mitogenic stimulation, response of splenocytes in a mixed lymphocyte reaction test, and specific response to a vaccination against tetanus toxoid. However, no significant changes were observed in 137-Cs contaminated animals as compared to control animals, even in 35 weeks-old animals. Overall, these results suggest that 137-Cs may accumulate over time in some organs such as the heart, the kidney, the femurs and muscles. However, our results also demonstrate that 137-Cs ingestion does not induce a significant modification of the immune system. This suggests that the pathologies associated with the immune system observed within populations living onto contaminated territories might not be attributed solely to the 137-Cs internal contamination.

The case of a 74-year-old female who developed toxic epidermal necrolysis (30% TBSA) is presented. Despite early, aggressive treatment, the patient developed severe would sepsis and multiple-system organ failure. The fulminant wound sepsis was preceded by early endotoxemia. Patient serum suppressed T lymphocyte blastogenesis in the mixed lymphocyte reaction test and neutrophil chemotaxis in vitro. Endotoxin removal (affinity chromatography) resulted in a reverse of serum suppressive activity against T lymphocytes but did not reverse inhibition of PMN chemotaxis. Circulating endotoxin levels remained detectable during the entire course while blood cultures remained negative. It is our belief that early endotoxemia (detected before clinical signs of would sepsis becomes apparent) leads to immunosuppression and other systemic complications.

We examined the autologous mixed lymphocyte reaction in human T-cell lymphotropic virus type I-associated myelopathy to elucidate the known increase in spontaneous proliferation of peripheral blood lymphocytes. Proliferative responses in the autologous mixed lymphocyte reaction test were significantly increased (34,205 cpm) in cells from 9 patients with the myelopathy, as compared with findings (18,695 cpm) in the control subjects. When non-T-cell fractions were depleted from autologous mixed lymphocyte reaction cultures, proliferative responses were completely suppressed in the control subjects, while proliferation of the peripheral blood lymphocytes from the groups with the myelopathy were not affected by depletion of non-T-cell fractions. The increase in spontaneous proliferation of peripheral blood lymphocytes in patients with the myelopathy is probably not related to an increase in autologous mixed lymphocyte reactions.